Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of...Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses.The most prevalent chronic inflammatory illness,rheumatoid arthritis(RA),is typified by persistent synovitis thatmakes it hard for the disease to go away on its own.Interestingly,a unique subset of eosinophils known as regulatory eosinophils has been found in RA patients’synovium,especially while the disease is in remission.Pro-resolving signatures of regulatory eosinophils in the synovium are distinct from those of their lung counterparts.The most recent research on eosinophils and their function in this disease pathogenesis is compiled in this review.Based on the role of regulatory eosinophils,a new pathological model of inflammation resolution in RA is proposed,and potential therapeutic strategies aimed at enhancing the action of regulatory eosinophils in RA are proposed.展开更多
Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease.These cells store in their specific granules numerous biological...Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease.These cells store in their specific granules numerous biologically active substances(cytotoxic cationic proteins, cytokines, growth factors, chemokines,enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease(IBD),when their cytotoxic granule proteins cause damage to host tissues. However,their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer(CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.展开更多
BACKGROUND: The effect of blood eosinophils(EOSs) on mortality in acute respiratory distress syndrome(ARDS) patients and whether corticosteroids affect this effect are unclear.METHODS: The Medical Information Mart for...BACKGROUND: The effect of blood eosinophils(EOSs) on mortality in acute respiratory distress syndrome(ARDS) patients and whether corticosteroids affect this effect are unclear.METHODS: The Medical Information Mart for Intensive Care III database(version 1.4) was used to extract data. Patients with ARDS were selected for inclusion. Cox regression models using the backward stepwise method and propensity score matching(PSM) were used to assess the relationship between blood EOS counts and 28-day mortality. RESULTS: A total of 2,567 patients with ARDS were included, and the 28-day mortality rate was 24.19%. The crude 28-day mortality was significantly lower in patients with EOS counts ≥2%(18.60% [85/457] vs. 25.40% [536/2,110], P=0.002) than in those with EOS counts <2%. In the Cox regression model, the EOS counts ≥2% showed a significant association with the decreased 28-day mortality(hazard ratio [HR] 0.731;95% confidence interval [95% CI] 0.581–0.921, P=0.008). In the corticosteroid non-use subgroup, EOS counts ≥2% was significantly related to decreased 28-day mortality(HR 0.697, 95% CI 0.535–0.909, P=0.008), but the result was not significant in the corticosteroid non-use subgroup model(P=0.860). A total of 457 well-matched pairs were obtained by a 1:1 matching algorithm after PSM. The 28-day mortality remained significantly lower in the EOS counts ≥2% group(18.60% [85/457] vs. 26.70% [122/457], P=0.003).CONCLUSIONS Higher EOS counts are related to lower 28-day mortality in ARDS patients, and this relationship can be counteracted by using corticosteroids.展开更多
There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation...There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.展开更多
Asthma is a chronic inflammatory disorder of the airways characterized by recurring episodes of reversible airway obstruction, hyper-responsiveness, wheezing, breathlessness and coughing. Clinical diagnosis of asthma ...Asthma is a chronic inflammatory disorder of the airways characterized by recurring episodes of reversible airway obstruction, hyper-responsiveness, wheezing, breathlessness and coughing. Clinical diagnosis of asthma is based on the pattern of clinical symptoms and pulmonary fuction tests. Asthma affectes 5% - 10% of the population and the number of worldwide cases is approximately 300 milliones. The incidence of this disease is increasing particulry in western countries [1]. It is the cause of a huge economic burden to national healthcare services. In a minority of cases, asthma is potentially fatal. After a period when fatalities appeared to be increasing [2], in recent years asthma-related mortality has progressively declined due to the develop- ment of specific asthma disease management programs, as well as the extensive use of in- haled corticosteroids [3]. Inflammation of the airways is a central component in asthma. In- flammation is associated with infliltration of the airway wall with eosinophiles and or neutron- philes mast cell degranulation and T cell active- tion. Other pathological features include, sub- basement membrane thickening, loss of epithet- lial cell integrity, goblet cells hyperplasia In- crease in airway smooth muscle mass. Eosino- phils are thought to be vital in the development of airway hyperreactivity, with the eosinophil cationic protein playing a crucial role [4]. The fact that treatment of asthma with corticos-teroids reduces eosinophils numbers and decreases airway reactivity further supports this hypothesis.展开更多
Chronic obstructive pulmonary disease(COPD)accounts for one of the major health and economic burdens worldwide.As a heterogeneous disease,the underlying inflammatory pattern of COPD differs from the previously thought...Chronic obstructive pulmonary disease(COPD)accounts for one of the major health and economic burdens worldwide.As a heterogeneous disease,the underlying inflammatory pattern of COPD differs from the previously thought neutrophil-dominated inflammation,with eosinophilic inflammation occupying approximately one third of stable COPD.Although the eosinophil(EOS)threshold associated with clinical relevance in patients with COPD is currently debated,eosinophil count can be used as a biomarker to guide treatment and to assess the risk of acute exacerbations of COPD,the efficacy of inhaled corticosteroids,and clinical outcomes.The purpose of this review is to describe the biological characteristics of eosinophils and the related research progress as clinical biomarkers.展开更多
Objective:To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein rnRNA in the bone marrow,peripheral blood and nasal lavage fluid.Mc...Objective:To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein rnRNA in the bone marrow,peripheral blood and nasal lavage fluid.Mctliods:Twenty-four BALB/c mice were randomly divided into the control group.PBS therapy group.siKNA therapy group and the CCR3 siRNA therapy group(n=6).Allergic rhinitis model were sensitized and stimulated by ovalbunfin,and CCR3 siKNA therapy group were administered with CCH3 transnasally before stimulated.The levels of the eosinophils CCR3.MBP.ECP and EPO in bone marrow,peripheral blood and nasal lavage fluid were detected by RT-PCR.Results:Compared to the control group and CCR3 siR.NA therapy group,the nasal mucosa of the PBS therapy group and siRNA therapy group developed epithalaxy.goblet cells hyperplasia,squamous epithelium metaplasia,epithelium necrosis,lamina propria and submucosa gland hyperplasia,vasodilatation,tissue edema,and the characterized eosinophil infiltration.RT-PCR indicated that the CCR3 rnRNA,MBP.ECP and EPC)expression in bone marrow,peripheral blood and nasal lavage fluid of the CCR3 siKNA therapy group was lower than the PBS therapy group and siR.NA therapy group(P<0.05).Conclusions:The RNA interference therapy to CCR3 by local administration pernasal can suppress the process of the development,migration and invasion of the allergic rhinitis eosinophil,thus can reduce the effect of eosinophils and then reduce the inflammation effect of the allergic rhinitis.It may be a new treatment for respiratory tract allergic inflammation.展开更多
BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is bei...BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.展开更多
The association between blood eosinophil(EOS)counts and arterial/venous throm-bosis is unclear.We aim to explore whether EOS count is a risk factor for throm-bosis.We searched several databases and preprint platforms ...The association between blood eosinophil(EOS)counts and arterial/venous throm-bosis is unclear.We aim to explore whether EOS count is a risk factor for throm-bosis.We searched several databases and preprint platforms using core terms‘eosinophil’,‘myocardial infarction’,‘ischemic stroke’,and‘venous thromboembo-lism’(VTE),among others.Studies comparing the odds ratios(ORs)or risk ratios(RRs)of EOSs with the abovementioned diseases were eligible.Overall,22 studies were included.A high EOS count was associated with acute coronary artery throm-bosis events(OR:1.23,95%CI:1.15-1.32),short-term cerebral infarction and mor-tality(RR:2.87,95%CI:1.49-5.51).The short-term risk of VTE was more common in patients with EOS-related diseases(RR:6.52,95%CI:2.42-17.54).For coronary artery disease,a high EOS count was a protective factor against 6-month to 1-year mortality(RR:0.56,95%CI:0.45-0.69)but was associated with long-term mortal-ity(RR:1.64,95%CI:1.25-2.14).Therefore,we conclude that for coronary artery thrombosis,EOS count is not associated with AMI events in general population.It may be associated with NSTEMI and STEMI in CAD patients,but more studies are needed to confirm this.In addition,EOS count is associated with an increased risk of both short-and long-term mortality but is not predictive of the composite end-points.For cerebral artery thrombosis,EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short-term prognosis.For VTEs,EOS count was a risk factor for some patients,especially those with acute-phase EOS-related diseases.展开更多
Objectives:This study aims to investigate the role of Sirt5 in regulating eosinophil maturation and activation,specifically focusing on primary eosinophils in mice at the genetic level.Additionally,the study aims to e...Objectives:This study aims to investigate the role of Sirt5 in regulating eosinophil maturation and activation,specifically focusing on primary eosinophils in mice at the genetic level.Additionally,the study aims to elucidate the underlying mechanism of Sirt5 in eosinophilic inflammation metabolism and identify potential drug targets for the treatment of chronic sinusitis.The findings of this study will provide new insights and a solid theoretical basis for the development of novel therapeutic strategies for eosinophilic chronic rhinosinusitis(eCRS).Methods:Our study investigated the role of Sirt5 gene expression in both non-eCRS and eCRS.We examined the correlation between Sirt5 gene expression and disease severity as well as eosinophil infiltration.Additionally,we utilized a mouse model of eCRS to assess the impact of Sirt5 gene deletion on the disease.To further understand the underlying mechanisms,we conducted experiments at the single-cell level using bone marrow-derived eosinophils.We validated our findings through in vitro culture of eosinophils and intervention experiments.Through these experiments,we aimed to elucidate how Sirt5 regulates target proteins and reshapes their related metabolic pathways.Results:There is a positive correlation between the severity of eCRS and the expression level of Sirt5 in nasal mucosa.Inhibiting Sirt5 expression can effectively alleviate the abnormal activation of eosinophils and the resulting inflammatory response in eCRS-affected nasal mucosa.Sirt5 exerts its influence on eosinophil metabolism by negatively regulating the succinylation level of pkm2,a critical gene in the amino acid biosynthesis pathway.Conclusions:The severity of eCRS is closely associated with the expression level of Sirt5.Sirt5 plays a negative regulatory role in the succinylation level of Pkm2 in eosinophils,thereby influencing metabolic remodeling and functional activation in eCRS.Investigating Sirt5 and its downstream metabolic pathways could offer valuable insights into the disease's pathogenesis and facilitate the development of targeted therapeutic strategies.This research holds significant implications for clinical practitioners involved in the diagnosis and treatment of patients with eCRS.展开更多
The novel interleukin(IL)-1 family cytokine IL-33 has been shown to activate T helper 2(Th2)lymphocytes,mast cells and basophils to produce an array of proinflammatory cytokines,as well as to mediate blood eosinophili...The novel interleukin(IL)-1 family cytokine IL-33 has been shown to activate T helper 2(Th2)lymphocytes,mast cells and basophils to produce an array of proinflammatory cytokines,as well as to mediate blood eosinophilia,IgE secretion and hypertrophy of airway epithelium in mice.In the present study,we characterized the activation of human eosinophils by IL-33,and investigated the underlying intracellular signaling mechanisms.IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule(ICAM)-1 on eosinophils,but it suppressed that of ICAM-3 and L-selectin.In addition,IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2.We found that IL33-mediated enhancement of survival,induction of adhesion molecules,and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor(NF)-KB,p38 mitogen-activated protein kinase(MAPK)and extracellular signal-regulated kinase(ERK)pathways.Furthermore,we compared the above IL-33 activities with two structurally and functionally related cytokines,IL-1 B and IL-18.IL-1β,but not IL-18,markedly upregulated cell surface expression of ICAM-1.IL-1βand IL-18 also significantly enhanced eosinophil survival,and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB,p38 MAPK and ERK pathways.Synergistic efects on the release of IL-6 were also observed in combined treatment withIL-1B,IL-18 and IL-33.Taken together,our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation.展开更多
Background Asthma is a chronic airway disease with inflammation characterized by physiological changes （airway hyper-responsiveness, AHR） and pathological changes （inflammatory cells infiltration and mucus product...Background Asthma is a chronic airway disease with inflammation characterized by physiological changes （airway hyper-responsiveness, AHR） and pathological changes （inflammatory cells infiltration and mucus production）. Eosinophils play a key role in the allergic inflammation. But the causative relationship between eosinophils and airway inflammation is hard to prove. One of the reasons is lack of activation marker of murine eosinophils. We investigated the expression of CD69 on murine eosinophils in vitro, the relationship between the expression of CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on airway inflammation in asthmatic mice. Methods Eosinophils from peripheral blood of IL-5 transgenic mice （NJ.1638） were purified. Mice were divided into five groups： wild type mice sensitized and challenged with saline （WS group）, wild type mice sensitized and challenged with ovalbumin （WO group）, IL-5^-/- mice sensitized and challenged with saline and transferred with purified eosinophils （ISE group）, IL-5^-/- mice sensitized and challenged with OVA and transferred with purified eosinophils （IOE group）, IL-5^-/- mice sensitized and challenged with OVA and transferred with purified eosinophils, pretreated with anti CD4 monoclonal antibody （IOE＋antiCD4mAb group）. IL-5^-/- mice were sensitized with OVA at day 0 and day 14, then challenged with OVA aerosol. On days 24, 25, 26 and 27 purified eosinophils were transferred intratracheally to IL-5^-/- mice. On day 28, blood and BALF were collected and CD69 expression on eosinophils measured by flowcytometry. Results Purified eosinophils did not express CD69. But eosinophils cultured with PMA＋MA, IFN- T, IL-5 or GM-CSF expressed CD69 strongly. Eosinophils from blood of WO, WS group did not express CD69 at all. The numbers of eosinophils in BALF of WO group, IOE group, ISE group and IOE＋antiCD4mAb group were significantly higher than in mice of WS group which did not have eosinophils at all. CD69 expression on eosinophils in BALF of IOE and WO groups was strong. Eosinophils in BALF of ISE and IOE＋antiCDmAb groups did not express CD69. The mucus production result was similar to CD69 expression. There were eosinophils infiltration in lung slides of all groups except WS group. Conclusion Activation in airway of eosinophils could directly lead to airway inflammation.展开更多
Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain （NOD）-Iike receptors （NLRs）. We elucidated the NOD1 and NOD2-mediated ...Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain （NOD）-Iike receptors （NLRs）. We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand 7-D-glutamyl-meso-diaminopimelic acid （iE-DAP） and NOD2 ligand muramyl dipeptide （MDP）. However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule （ICAM）-I on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system （all P〈0.05）. Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-KB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 （Th2） cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice （all P〈0.05）. This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.展开更多
The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mech...The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.展开更多
Objective To explore the significance of protein kinase C (PKC) in proliferation and infiltration of eosinophils in nasal polyps. Methods With in situ hybridization and immunohistochemistry staining methods,PKC,pro-ap...Objective To explore the significance of protein kinase C (PKC) in proliferation and infiltration of eosinophils in nasal polyps. Methods With in situ hybridization and immunohistochemistry staining methods,PKC,pro-apoptotic,and anti-apoptotic gene (Bax,bcl-2 ) expressions were measured in nasal polyp tissues from 26 patients and inferior turbinate mucosa tissues (ITMTs) from 20 healthy persons. The May-Grünwald-Giemsa (MGG) staining method was used to identify eosinophils. Results In eosinophils,the positive cell expressive rates of Bcl-2 mRNA and its protein were significantly higher in the group with nasal polyps than in the ITMT group ( P <0.01). Although the positive cell expressive rate of Bax mRNA and associated protein were a little higher in the group with nasal polyp tissues than in the ITMT group,the difference was not significant ( P >0.05). There was PKC expression in the eosinophils of 26 cases of nasal polyps,but occasional PKC expression in 7 of 20 ITMT cases. In the two groups,PKC positive cell expression was significantly different,and the expression of PKC and bcl-2 mRNA as well as associated protein in eosinophils of nasal polyps showed a remarkably positive relationship ( r 1=0.0875,r 2=0.0823,P <0.01). Conclusions Increased PKC expression in eosinophils of nasal polyp tissues is closely associated with apoptosis inhibition,and it is presumed that eosinophil apoptosis inhibition in nasal polyp tissues is obtained by activation of the PKC signal transduction pathway.展开更多
Objective To investigate the relationship between intercellular adhesion molecule 1 (ICAM 1) and the accumulation of eosinophils in nasal polyp tissue to better understand the mechanism of airway eosinophilic infla...Objective To investigate the relationship between intercellular adhesion molecule 1 (ICAM 1) and the accumulation of eosinophils in nasal polyp tissue to better understand the mechanism of airway eosinophilic inflammation.Methods The expression of ICAM 1 and its natural ligand, lymphocyte function associated antigen 1 (LFA 1), in normal nasal mucosa from 6 controls and in nasal polyp tissue from 19 patients with nasal polyposis were determined with immunohistochemistry. With dual immunohistochemistry and May Griünwald Giemsa stain (MGG), the expression of LFA 1 and infiltrating eosinophils in nasal polyp tissue was observed.Results The expression of ICAM 1 and LFA 1 was stronger in the nasal polyp tissue than in normal nasal mucosa. There was a positive relationship between the infiltration of eosinophils and the expression of LFA 1 on eosinophils.Conclusion Accumulation of eosinophils in nasal polyp tissue is associated with the counter effect between adhesion molecules and its ligand on eosinophils.展开更多
In a recent study published in Nature,Gurtner and colleagues identify active eosinophils(A-Eos)as eosinophil subset with anti-bacterial and immune regulatory functions during intestinal disease.1 Due to the combinatio...In a recent study published in Nature,Gurtner and colleagues identify active eosinophils(A-Eos)as eosinophil subset with anti-bacterial and immune regulatory functions during intestinal disease.1 Due to the combination of human singe cell transcip-tomics with pre-clinical experimental studies,the authors suggest eosinophils as promising targets for clinical intervention in inflammatory bowel disease(IBD).Eosinophils are known to exhibit versatile functions at mucosal surfaces.Thus,they can sustain the intestinal epithelial barrier as well as intestinal tissue architecture,communicate with other cell subsets and regulate local immune responses.2 However,despite having been associated with a panoply of different diseases including eosinophilic esophagitis or IBD,3 their role and plasticity in gastrointestinal disorders have not been well characterized.展开更多
Background Antigen loaded eosinophils (EOSs) instilled intratracheally into mice were capable of inducing Th2 type cytokine production in the draining lymph nodes The aim of the present study was to evaluate whet...Background Antigen loaded eosinophils (EOSs) instilled intratracheally into mice were capable of inducing Th2 type cytokine production in the draining lymph nodes The aim of the present study was to evaluate whether EOSs within the tracheobronchial lumen can stimulate Th2 cell expansion in the lung tissues Methods Airway EOSs were recovered from ovalbumin sensitized and challenged BALB/c mice, these EOSs were then cocultured with CD4 + cells isolated from sensitized mice in the absence or presence of anti CD80 or/and CD86 monoclonal antibodies Airway EOSs were instilled into the trachea of sensitized mice. At the day 3 thereafter, the lung tissues were removed and prepared into cell suspensions for culture Cell free culture supernatants were collected for detection of cytokines Results Airway EOSs functioned as CD80 and CD86 dependent antigen presenting cells to stimulate lung CD4 + lymphocytes to produce interleukin 4, interleukin 5 and interleukin 13, but not interferon γ in in vitro assay When instilled intratracheally in sensitized recipient mice, airway EOSs primed lung Th2 cells in vivo for interleukin 4, interleukin 5 and interleukin 13, but not interferon γ, production during the in vitro culture that was also CD80 and CD86 dependent Conclusion EOSs within the lumina of airways could process inhaled antigen and function in vitro and in vivo as antigen presenting cells to promote expansion of Th2 cells in the lungs展开更多
Background Primary eosinophilic gastrointestinal disorders(EGIDs)constitute chronic allergic inflammation.The number of eosinophils is one of the diagnostic criteria;more than 20 eosinophils per high-power field(HPF)i...Background Primary eosinophilic gastrointestinal disorders(EGIDs)constitute chronic allergic inflammation.The number of eosinophils is one of the diagnostic criteria;more than 20 eosinophils per high-power field(HPF)in the gastrointestinal(GI)tract are considered abnormal in Japan.However,the quantity of eosinophils considered normal varies according to anatomical location and geographical region;such values have not been reported in Japanese pediatric patients,nor have the numbers of lymphocytes in the normal pediatric stomach.To establish a reference for defining diagnostic criteria for EGIDs,we evaluated the number of eosinophils in the normal Japanese pediatric GI tract.Methods We examined 131 biopsy cases without significant clinical history,endoscopic abnormality,or histological abnor-mality.Immunohistochemical analysis of CD3 and CD20 was performed.Results The mean eosinophil density was highest in the cecum(49.5±22.4 per HPF).Counts of more than 20 eosinophils per HPF were observed in the duodenum[bulb(20.0±9.6)and second portion(30.0±15.8)],terminal ileum(38.3±22.7),cecum(49.5±22.4),ascending colon(42.3±25.3),transverse colon(29.4±17.0),and descending colon(32.2±17.9).Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum;a count of fewer than one eosinophil per HPF was observed in the esophagus.More than 100 CD3-positive T cells per HPF were observed in the stomach.Conclusions The mean numbers of eosinophils in the bowel were greater than 20 per HPF.For Japanese pediatrics,the cur-rent threshold eosinophil count should be revised.展开更多
基金supported by NIH grants to M Bukrinsky P30 AI117970by the“Creation of Experimental Laboratories in the Natural Sciences Program”and Basic Research Program at the Higher School of Economics University.
文摘Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses.The most prevalent chronic inflammatory illness,rheumatoid arthritis(RA),is typified by persistent synovitis thatmakes it hard for the disease to go away on its own.Interestingly,a unique subset of eosinophils known as regulatory eosinophils has been found in RA patients’synovium,especially while the disease is in remission.Pro-resolving signatures of regulatory eosinophils in the synovium are distinct from those of their lung counterparts.The most recent research on eosinophils and their function in this disease pathogenesis is compiled in this review.Based on the role of regulatory eosinophils,a new pathological model of inflammation resolution in RA is proposed,and potential therapeutic strategies aimed at enhancing the action of regulatory eosinophils in RA are proposed.
文摘Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and disease.These cells store in their specific granules numerous biologically active substances(cytotoxic cationic proteins, cytokines, growth factors, chemokines,enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease(IBD),when their cytotoxic granule proteins cause damage to host tissues. However,their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer(CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.
文摘BACKGROUND: The effect of blood eosinophils(EOSs) on mortality in acute respiratory distress syndrome(ARDS) patients and whether corticosteroids affect this effect are unclear.METHODS: The Medical Information Mart for Intensive Care III database(version 1.4) was used to extract data. Patients with ARDS were selected for inclusion. Cox regression models using the backward stepwise method and propensity score matching(PSM) were used to assess the relationship between blood EOS counts and 28-day mortality. RESULTS: A total of 2,567 patients with ARDS were included, and the 28-day mortality rate was 24.19%. The crude 28-day mortality was significantly lower in patients with EOS counts ≥2%(18.60% [85/457] vs. 25.40% [536/2,110], P=0.002) than in those with EOS counts <2%. In the Cox regression model, the EOS counts ≥2% showed a significant association with the decreased 28-day mortality(hazard ratio [HR] 0.731;95% confidence interval [95% CI] 0.581–0.921, P=0.008). In the corticosteroid non-use subgroup, EOS counts ≥2% was significantly related to decreased 28-day mortality(HR 0.697, 95% CI 0.535–0.909, P=0.008), but the result was not significant in the corticosteroid non-use subgroup model(P=0.860). A total of 457 well-matched pairs were obtained by a 1:1 matching algorithm after PSM. The 28-day mortality remained significantly lower in the EOS counts ≥2% group(18.60% [85/457] vs. 26.70% [122/457], P=0.003).CONCLUSIONS Higher EOS counts are related to lower 28-day mortality in ARDS patients, and this relationship can be counteracted by using corticosteroids.
文摘There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia(FD).Importantly,inflammation may serve as a mediator between psychologic and physiologic functions.This manuscript reviews the literature implicating two inflammatory cell types,mast cells and eosinophils,in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD.There are a number of inciting events which may initiate an inflammatory response,and the subsequent recruitment and activation of mast cells and eosinophils.These include internal triggers such as stress and anxiety,as well as external triggers such as microbes and allergens.Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils.Evidence exists to suggest that combining "anti-inflammatory" medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD.
文摘Asthma is a chronic inflammatory disorder of the airways characterized by recurring episodes of reversible airway obstruction, hyper-responsiveness, wheezing, breathlessness and coughing. Clinical diagnosis of asthma is based on the pattern of clinical symptoms and pulmonary fuction tests. Asthma affectes 5% - 10% of the population and the number of worldwide cases is approximately 300 milliones. The incidence of this disease is increasing particulry in western countries [1]. It is the cause of a huge economic burden to national healthcare services. In a minority of cases, asthma is potentially fatal. After a period when fatalities appeared to be increasing [2], in recent years asthma-related mortality has progressively declined due to the develop- ment of specific asthma disease management programs, as well as the extensive use of in- haled corticosteroids [3]. Inflammation of the airways is a central component in asthma. In- flammation is associated with infliltration of the airway wall with eosinophiles and or neutron- philes mast cell degranulation and T cell active- tion. Other pathological features include, sub- basement membrane thickening, loss of epithet- lial cell integrity, goblet cells hyperplasia In- crease in airway smooth muscle mass. Eosino- phils are thought to be vital in the development of airway hyperreactivity, with the eosinophil cationic protein playing a crucial role [4]. The fact that treatment of asthma with corticos-teroids reduces eosinophils numbers and decreases airway reactivity further supports this hypothesis.
文摘Chronic obstructive pulmonary disease(COPD)accounts for one of the major health and economic burdens worldwide.As a heterogeneous disease,the underlying inflammatory pattern of COPD differs from the previously thought neutrophil-dominated inflammation,with eosinophilic inflammation occupying approximately one third of stable COPD.Although the eosinophil(EOS)threshold associated with clinical relevance in patients with COPD is currently debated,eosinophil count can be used as a biomarker to guide treatment and to assess the risk of acute exacerbations of COPD,the efficacy of inhaled corticosteroids,and clinical outcomes.The purpose of this review is to describe the biological characteristics of eosinophils and the related research progress as clinical biomarkers.
基金supported by the National Natural Science Fund Project in China(grant No.:81060084)Jiangxi Provincial Natural Science Fund Project in China(grant No.:2010gzy0251)+1 种基金Jiangxi Provincial Health Department Project in China(grant No.:20131059)Jiangxi Provincial Department of Science and Technology Project in China(grant No.:20133BBG70071)
文摘Objective:To observe the clinical manifestations of allergic rhinitis mice and the expression changes of the eosinophils CCR3 and the granule protein rnRNA in the bone marrow,peripheral blood and nasal lavage fluid.Mctliods:Twenty-four BALB/c mice were randomly divided into the control group.PBS therapy group.siKNA therapy group and the CCR3 siRNA therapy group(n=6).Allergic rhinitis model were sensitized and stimulated by ovalbunfin,and CCR3 siKNA therapy group were administered with CCH3 transnasally before stimulated.The levels of the eosinophils CCR3.MBP.ECP and EPO in bone marrow,peripheral blood and nasal lavage fluid were detected by RT-PCR.Results:Compared to the control group and CCR3 siR.NA therapy group,the nasal mucosa of the PBS therapy group and siRNA therapy group developed epithalaxy.goblet cells hyperplasia,squamous epithelium metaplasia,epithelium necrosis,lamina propria and submucosa gland hyperplasia,vasodilatation,tissue edema,and the characterized eosinophil infiltration.RT-PCR indicated that the CCR3 rnRNA,MBP.ECP and EPC)expression in bone marrow,peripheral blood and nasal lavage fluid of the CCR3 siKNA therapy group was lower than the PBS therapy group and siR.NA therapy group(P<0.05).Conclusions:The RNA interference therapy to CCR3 by local administration pernasal can suppress the process of the development,migration and invasion of the allergic rhinitis eosinophil,thus can reduce the effect of eosinophils and then reduce the inflammation effect of the allergic rhinitis.It may be a new treatment for respiratory tract allergic inflammation.
文摘BACKGROUND Eosinophilic esophagitis(EoE)is an eosinophilic-predominant inflammation of the esophagus diagnosed by upper endoscopy and biopsies.A non-invasive and cost-effective alternative for management of EoE is being researched.Previous studies assessing utility of fractional exhaled nitric oxide(FeNO)in EoE were low powered.None investigated the contribution of eosinophilic inflammation of the stomach and duodenum to FeNO.AIM To assess the utility of FeNO as a non-invasive biomarker of esophageal eosinophilic inflammation for monitoring disease activity.METHODS Patients aged 6-21 years undergoing scheduled upper endoscopy with biopsy for suspected EoE were recruited in our observational study.Patients on steroids and with persistent asthma requiring daily controller medication were excluded.FeNO measurements were obtained in duplicate using a chemiluminescence nitric oxide analyzer(NIOX MINO,Aerocrine,Inc.;Stockholm,Sweden)prior to endoscopy.Based on the esophageal peak eosinophil count(PEC)/high power field on biopsy,patients were classified as EoE(PEC≥15)or control(PEC≤14).Mean FeNO levels were correlated with presence or absence of EoE,eosinophil counts on esophageal biopsy,and abnormal downstream eosinophilia in the stomach(PEC≥10)and duodenum(PEC≥20).Wilcoxon rank-sum test,Spearman correlation,and logistic regression were used for analysis.P value<0.05 was considered significant.RESULTS We recruited a total of 134 patients,of which 45 were diagnosed with EoE by histopathology.The median interquartile range FeNO level was 17 parts per billion(11-37,range:7-81)in the EoE group and 12 parts per billion(8-19,range:5-71)in the control group.After adjusting for atopic diseases,EoE patients had significantly higher FeNO levels as compared to patients without EoE(Z=3.33,P<0.001).A weak yet statistically significant positive association was found between the number of esophageal eosinophils and FeNO levels(r=0.30,P<0.005).On subgroup analysis within the EoE cohort,higher FeNO levels were noted in patients with abnormal gastric(n=23,18 vs 15)and duodenal eosinophilia(n=28,21 vs 14);however,the difference was not statistically significant.CONCLUSION After ruling out atopy as possible confounder,we found significantly higher FeNO levels in the EoE cohort than in the control group.
基金National Natural Science Foundation of China,Grant/Award Number:81700045 and 82000059Program of Shanghai Pulmonary Hospital,Grant/Award Number:FKLY20005Three-year Action Plan to Promote Clinical Skills and Clinical Innovation in Municipal Hospitals,Grant/Award Number:SHDC2020CR4021。
文摘The association between blood eosinophil(EOS)counts and arterial/venous throm-bosis is unclear.We aim to explore whether EOS count is a risk factor for throm-bosis.We searched several databases and preprint platforms using core terms‘eosinophil’,‘myocardial infarction’,‘ischemic stroke’,and‘venous thromboembo-lism’(VTE),among others.Studies comparing the odds ratios(ORs)or risk ratios(RRs)of EOSs with the abovementioned diseases were eligible.Overall,22 studies were included.A high EOS count was associated with acute coronary artery throm-bosis events(OR:1.23,95%CI:1.15-1.32),short-term cerebral infarction and mor-tality(RR:2.87,95%CI:1.49-5.51).The short-term risk of VTE was more common in patients with EOS-related diseases(RR:6.52,95%CI:2.42-17.54).For coronary artery disease,a high EOS count was a protective factor against 6-month to 1-year mortality(RR:0.56,95%CI:0.45-0.69)but was associated with long-term mortal-ity(RR:1.64,95%CI:1.25-2.14).Therefore,we conclude that for coronary artery thrombosis,EOS count is not associated with AMI events in general population.It may be associated with NSTEMI and STEMI in CAD patients,but more studies are needed to confirm this.In addition,EOS count is associated with an increased risk of both short-and long-term mortality but is not predictive of the composite end-points.For cerebral artery thrombosis,EOS count may be associated with cerebral infarction and could lead to an increased risk of poor short-term prognosis.For VTEs,EOS count was a risk factor for some patients,especially those with acute-phase EOS-related diseases.
基金funded by the National Natural Science Foundation of China:81541038,81670905,81870702.
文摘Objectives:This study aims to investigate the role of Sirt5 in regulating eosinophil maturation and activation,specifically focusing on primary eosinophils in mice at the genetic level.Additionally,the study aims to elucidate the underlying mechanism of Sirt5 in eosinophilic inflammation metabolism and identify potential drug targets for the treatment of chronic sinusitis.The findings of this study will provide new insights and a solid theoretical basis for the development of novel therapeutic strategies for eosinophilic chronic rhinosinusitis(eCRS).Methods:Our study investigated the role of Sirt5 gene expression in both non-eCRS and eCRS.We examined the correlation between Sirt5 gene expression and disease severity as well as eosinophil infiltration.Additionally,we utilized a mouse model of eCRS to assess the impact of Sirt5 gene deletion on the disease.To further understand the underlying mechanisms,we conducted experiments at the single-cell level using bone marrow-derived eosinophils.We validated our findings through in vitro culture of eosinophils and intervention experiments.Through these experiments,we aimed to elucidate how Sirt5 regulates target proteins and reshapes their related metabolic pathways.Results:There is a positive correlation between the severity of eCRS and the expression level of Sirt5 in nasal mucosa.Inhibiting Sirt5 expression can effectively alleviate the abnormal activation of eosinophils and the resulting inflammatory response in eCRS-affected nasal mucosa.Sirt5 exerts its influence on eosinophil metabolism by negatively regulating the succinylation level of pkm2,a critical gene in the amino acid biosynthesis pathway.Conclusions:The severity of eCRS is closely associated with the expression level of Sirt5.Sirt5 plays a negative regulatory role in the succinylation level of Pkm2 in eosinophils,thereby influencing metabolic remodeling and functional activation in eCRS.Investigating Sirt5 and its downstream metabolic pathways could offer valuable insights into the disease's pathogenesis and facilitate the development of targeted therapeutic strategies.This research holds significant implications for clinical practitioners involved in the diagnosis and treatment of patients with eCRS.
基金This study was supported by Research Grant Committee General Research Fund,Hong Kong(Project code:CU08757,principal investigator:CK Wong,co-investigator:CWK Lam).
文摘The novel interleukin(IL)-1 family cytokine IL-33 has been shown to activate T helper 2(Th2)lymphocytes,mast cells and basophils to produce an array of proinflammatory cytokines,as well as to mediate blood eosinophilia,IgE secretion and hypertrophy of airway epithelium in mice.In the present study,we characterized the activation of human eosinophils by IL-33,and investigated the underlying intracellular signaling mechanisms.IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule(ICAM)-1 on eosinophils,but it suppressed that of ICAM-3 and L-selectin.In addition,IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2.We found that IL33-mediated enhancement of survival,induction of adhesion molecules,and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor(NF)-KB,p38 mitogen-activated protein kinase(MAPK)and extracellular signal-regulated kinase(ERK)pathways.Furthermore,we compared the above IL-33 activities with two structurally and functionally related cytokines,IL-1 B and IL-18.IL-1β,but not IL-18,markedly upregulated cell surface expression of ICAM-1.IL-1βand IL-18 also significantly enhanced eosinophil survival,and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-κB,p38 MAPK and ERK pathways.Synergistic efects on the release of IL-6 were also observed in combined treatment withIL-1B,IL-18 and IL-33.Taken together,our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation.
基金This work was partially supported by the National Natural Science Foundation of China (No. 30570807).
文摘Background Asthma is a chronic airway disease with inflammation characterized by physiological changes （airway hyper-responsiveness, AHR） and pathological changes （inflammatory cells infiltration and mucus production）. Eosinophils play a key role in the allergic inflammation. But the causative relationship between eosinophils and airway inflammation is hard to prove. One of the reasons is lack of activation marker of murine eosinophils. We investigated the expression of CD69 on murine eosinophils in vitro, the relationship between the expression of CD69 on eosinophils from peripheral blood and bronchoalveolar lavage fluid and on airway inflammation in asthmatic mice. Methods Eosinophils from peripheral blood of IL-5 transgenic mice （NJ.1638） were purified. Mice were divided into five groups： wild type mice sensitized and challenged with saline （WS group）, wild type mice sensitized and challenged with ovalbumin （WO group）, IL-5^-/- mice sensitized and challenged with saline and transferred with purified eosinophils （ISE group）, IL-5^-/- mice sensitized and challenged with OVA and transferred with purified eosinophils （IOE group）, IL-5^-/- mice sensitized and challenged with OVA and transferred with purified eosinophils, pretreated with anti CD4 monoclonal antibody （IOE＋antiCD4mAb group）. IL-5^-/- mice were sensitized with OVA at day 0 and day 14, then challenged with OVA aerosol. On days 24, 25, 26 and 27 purified eosinophils were transferred intratracheally to IL-5^-/- mice. On day 28, blood and BALF were collected and CD69 expression on eosinophils measured by flowcytometry. Results Purified eosinophils did not express CD69. But eosinophils cultured with PMA＋MA, IFN- T, IL-5 or GM-CSF expressed CD69 strongly. Eosinophils from blood of WO, WS group did not express CD69 at all. The numbers of eosinophils in BALF of WO group, IOE group, ISE group and IOE＋antiCD4mAb group were significantly higher than in mice of WS group which did not have eosinophils at all. CD69 expression on eosinophils in BALF of IOE and WO groups was strong. Eosinophils in BALF of ISE and IOE＋antiCDmAb groups did not express CD69. The mucus production result was similar to CD69 expression. There were eosinophils infiltration in lung slides of all groups except WS group. Conclusion Activation in airway of eosinophils could directly lead to airway inflammation.
文摘Key intracytosolic pattern recognition receptors of innate immunity against bacterial infections are nucleotide-binding oligomerization domain （NOD）-Iike receptors （NLRs）. We elucidated the NOD1 and NOD2-mediated activation of human eosinophils, the principal effector cells for allergic inflammation, upon interacting with human bronchial epithelial BEAS-2B cells in allergic asthma. Eosinophils constitutively expressed NOD1,2 but exhibited nonsignificant responses to release chemokines upon the stimulation by NOD1 ligand 7-D-glutamyl-meso-diaminopimelic acid （iE-DAP） and NOD2 ligand muramyl dipeptide （MDP）. However, iE-DAP and MDP could significantly upregulate cell surface expression of CD18 and intercellular adhesion molecule （ICAM）-I on eosinophils and ICAM-1 on BEAS-2B cells, as well as induce chemokines CCL2 and CXCL8 release in the coculture system （all P〈0.05）. Both eosinophils and BEAS-2B cells were the main source for CXCL8 and CCL2 release in the coculture system upon iE-DAP or MDP stimulation. Direct interaction between eosinophils and BEAS-2B cells is responsible for CCL2 release, and soluble mediators are implicated in CXCL8 release. ERK and NF-KB play regulatory roles for the expression of adhesion molecules and chemokines in coculture. Treatment with NOD1,2 ligand could induce the subepithelial fibrosis and significantly enhance the serum concentration of total IgE, chemokine CCL5 for eosinophils and T helper type 2 （Th2） cells and asthma Th2 cytokine IL-13 in bronchoalveolar lavage fluid of ovalbumin-sensitized allergic asthmatic mice （all P〈0.05）. This study provides further evidence of bacterial infection-mediated activation of NOD1,2 in triggering allergic asthma via the activation of eosinophils interacting with bronchial epithelial cells at inflammatory airway.
文摘The skin of patients with atopic dermatitis （AD） has a unique predisposition for colonization by Staphylococcus aureus （S. aureus）, which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 （NOD2） and toll-like receptor 2 （TLR2） ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions, Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil-fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway bv which S. aureus contributes to the DathoDhvsiology of AD.
文摘Objective To explore the significance of protein kinase C (PKC) in proliferation and infiltration of eosinophils in nasal polyps. Methods With in situ hybridization and immunohistochemistry staining methods,PKC,pro-apoptotic,and anti-apoptotic gene (Bax,bcl-2 ) expressions were measured in nasal polyp tissues from 26 patients and inferior turbinate mucosa tissues (ITMTs) from 20 healthy persons. The May-Grünwald-Giemsa (MGG) staining method was used to identify eosinophils. Results In eosinophils,the positive cell expressive rates of Bcl-2 mRNA and its protein were significantly higher in the group with nasal polyps than in the ITMT group ( P <0.01). Although the positive cell expressive rate of Bax mRNA and associated protein were a little higher in the group with nasal polyp tissues than in the ITMT group,the difference was not significant ( P >0.05). There was PKC expression in the eosinophils of 26 cases of nasal polyps,but occasional PKC expression in 7 of 20 ITMT cases. In the two groups,PKC positive cell expression was significantly different,and the expression of PKC and bcl-2 mRNA as well as associated protein in eosinophils of nasal polyps showed a remarkably positive relationship ( r 1=0.0875,r 2=0.0823,P <0.01). Conclusions Increased PKC expression in eosinophils of nasal polyp tissues is closely associated with apoptosis inhibition,and it is presumed that eosinophil apoptosis inhibition in nasal polyp tissues is obtained by activation of the PKC signal transduction pathway.
文摘Objective To investigate the relationship between intercellular adhesion molecule 1 (ICAM 1) and the accumulation of eosinophils in nasal polyp tissue to better understand the mechanism of airway eosinophilic inflammation.Methods The expression of ICAM 1 and its natural ligand, lymphocyte function associated antigen 1 (LFA 1), in normal nasal mucosa from 6 controls and in nasal polyp tissue from 19 patients with nasal polyposis were determined with immunohistochemistry. With dual immunohistochemistry and May Griünwald Giemsa stain (MGG), the expression of LFA 1 and infiltrating eosinophils in nasal polyp tissue was observed.Results The expression of ICAM 1 and LFA 1 was stronger in the nasal polyp tissue than in normal nasal mucosa. There was a positive relationship between the infiltration of eosinophils and the expression of LFA 1 on eosinophils.Conclusion Accumulation of eosinophils in nasal polyp tissue is associated with the counter effect between adhesion molecules and its ligand on eosinophils.
基金The German Research Foundation(DFG-CRC1181-project number C04 and DFG-MA 2621/5-1)the Sino German Center Mobility Programme(M-693)+1 种基金the Staedtler Stiftung(23/14)the Johannes and Frieda Marohn Stiftung(Alz/Iko-Matt/2022)supported this research.
文摘In a recent study published in Nature,Gurtner and colleagues identify active eosinophils(A-Eos)as eosinophil subset with anti-bacterial and immune regulatory functions during intestinal disease.1 Due to the combination of human singe cell transcip-tomics with pre-clinical experimental studies,the authors suggest eosinophils as promising targets for clinical intervention in inflammatory bowel disease(IBD).Eosinophils are known to exhibit versatile functions at mucosal surfaces.Thus,they can sustain the intestinal epithelial barrier as well as intestinal tissue architecture,communicate with other cell subsets and regulate local immune responses.2 However,despite having been associated with a panoply of different diseases including eosinophilic esophagitis or IBD,3 their role and plasticity in gastrointestinal disorders have not been well characterized.
基金ThisstudywassupportedbyresearchgrantfromNationalNaturalScienceFoundationofChina (No 30 2 6 0 0 4 1 ) andbyresearchgrantsfromNaturalScienceFoundationofGuangxiZhuangAutonomousZoneChina (No 0 2 2 90 2 3)
文摘Background Antigen loaded eosinophils (EOSs) instilled intratracheally into mice were capable of inducing Th2 type cytokine production in the draining lymph nodes The aim of the present study was to evaluate whether EOSs within the tracheobronchial lumen can stimulate Th2 cell expansion in the lung tissues Methods Airway EOSs were recovered from ovalbumin sensitized and challenged BALB/c mice, these EOSs were then cocultured with CD4 + cells isolated from sensitized mice in the absence or presence of anti CD80 or/and CD86 monoclonal antibodies Airway EOSs were instilled into the trachea of sensitized mice. At the day 3 thereafter, the lung tissues were removed and prepared into cell suspensions for culture Cell free culture supernatants were collected for detection of cytokines Results Airway EOSs functioned as CD80 and CD86 dependent antigen presenting cells to stimulate lung CD4 + lymphocytes to produce interleukin 4, interleukin 5 and interleukin 13, but not interferon γ in in vitro assay When instilled intratracheally in sensitized recipient mice, airway EOSs primed lung Th2 cells in vivo for interleukin 4, interleukin 5 and interleukin 13, but not interferon γ, production during the in vitro culture that was also CD80 and CD86 dependent Conclusion EOSs within the lumina of airways could process inhaled antigen and function in vitro and in vivo as antigen presenting cells to promote expansion of Th2 cells in the lungs
文摘Background Primary eosinophilic gastrointestinal disorders(EGIDs)constitute chronic allergic inflammation.The number of eosinophils is one of the diagnostic criteria;more than 20 eosinophils per high-power field(HPF)in the gastrointestinal(GI)tract are considered abnormal in Japan.However,the quantity of eosinophils considered normal varies according to anatomical location and geographical region;such values have not been reported in Japanese pediatric patients,nor have the numbers of lymphocytes in the normal pediatric stomach.To establish a reference for defining diagnostic criteria for EGIDs,we evaluated the number of eosinophils in the normal Japanese pediatric GI tract.Methods We examined 131 biopsy cases without significant clinical history,endoscopic abnormality,or histological abnor-mality.Immunohistochemical analysis of CD3 and CD20 was performed.Results The mean eosinophil density was highest in the cecum(49.5±22.4 per HPF).Counts of more than 20 eosinophils per HPF were observed in the duodenum[bulb(20.0±9.6)and second portion(30.0±15.8)],terminal ileum(38.3±22.7),cecum(49.5±22.4),ascending colon(42.3±25.3),transverse colon(29.4±17.0),and descending colon(32.2±17.9).Counts of fewer than 10 eosinophils per HPF were observed in the stomach and rectum;a count of fewer than one eosinophil per HPF was observed in the esophagus.More than 100 CD3-positive T cells per HPF were observed in the stomach.Conclusions The mean numbers of eosinophils in the bowel were greater than 20 per HPF.For Japanese pediatrics,the cur-rent threshold eosinophil count should be revised.
