Objective Cationic antimicrobial protein of 37 kDa(CAP37),a neutrophil-derived protein originally identified for its antimicrobial activity,is now known to have many regulatory effects on host cells.However,its role i...Objective Cationic antimicrobial protein of 37 kDa(CAP37),a neutrophil-derived protein originally identified for its antimicrobial activity,is now known to have many regulatory effects on host cells.However,its role in the pathogenesis of chronic obstructive pulmonary disease(COPD)has not been studied.We therefore investigated the expression of CAP37 in COPD and its effects on airway structural cells,including bronchial epithelial cells,smooth muscle cells,and fibroblasts.Methods CAP37 was detected in the lung tissue,sputum,and plasma of COPD patients and the control subjects,as well as in the neutrophils stimulated by cigarette smoke extract(CSE).BEAS-2B cells,human bronchial smooth muscle cells(HBSMCs),and MRC-5 cells were treated with CAP37 or an anti-CAP37 antibody plus CAP37.Interleukin(IL)-6 and IL-8 were detected in the BEAS-2B cells.The cell proliferation was analyzed in the HBSMCs.Collagens were also detected in the MRC-5 cells.Results The expression of CAP37 was increased in the lung tissue and sputum supernatant of the COPD patients compared with the control subjects.The sputum supernatant CAP37 levels were inversely correlated with the forced expiratory volume in the first second percentage predicted in COPD.CAP37 was induced by CSE stimulation in the peripheral blood neutrophils from healthy non-smokers.CAP37 induced expression of IL-6 and IL-8 in BEAS-2B cells,and collagen expression of lung fibroblasts(MRC-5 cells).However,CAP37 did not significantly alter the proliferation of the HBSMCs.Conclusion Our findings indicated that neutrophil-derived CAP37 may be involved in airway inflammation and fibrosis in COPD via affecting the bronchial epithelial cells,and fibroblasts,thus suggesting a possible role of CAP37 in the development and progression of COPD.展开更多
PURPOSE: To investigate the role of cationic antimicrobial protein of Mr 37 kDa (CAP37) a neutrophil-derived inflammatory mediator on endothelial cell function. DATA SOURCES: Endothelial cells used in this study were ...PURPOSE: To investigate the role of cationic antimicrobial protein of Mr 37 kDa (CAP37) a neutrophil-derived inflammatory mediator on endothelial cell function. DATA SOURCES: Endothelial cells used in this study were obtained from human lung microvessels and rat aorta. The latter was a kind gift of Dr. Paula Grammas. The mono-mac 6 cell line used in this study was the generous gift of Dr. H.W. Loms Ziegler-Heitbrock. STUDY SELECTION AND DATA EXTRACTION: Endothelial cell proteins kinase C activity was determined by measuring calcium- and phospholipid-dependent phosphorylation of histone. Endothelial cell migration was determined using Costar Transwell apparatus. Cell surface expression of adhesion molecules, ICAM-1 and PECAM-1 was determined using flow cytometry. RT-PCR was used to amplify the CAP37 from endothelial cells treated with LPS. RESULTS: We demonstrated that CAP37 which was originally identified as having potent antimicrobial activity and chemotactic activity for monocytes was capable of modulating endothelial cell functions. CAP37 activated endothelial cell protein kinase C in a dose- and time-dependent fashion. Importantly CAP37 increased the adhesive properties of the endothelium for monocytes. CAP37 upregulated the well known adhesion molecules, ICAM-1 and PECAM-1 in a dose- and time-dependent manner. In addition, CAP37 promoted endothelial cell migration. Further investigations indicated that CAP37 was induced in endothelial cells in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 alpha as well as inflammatory mediators such as lipopolysaccharide. Unstimulated endothelial cells did not constitutively express CAP37. The cDNA sequence of endothelial CAP37 was determined and found to be highly homologous to the sequence obtained for neutrophil-derived CAP37. CONCLUSIONS: Our studies strongly suggest that CAP37 plays a pivotal role in monocyte-endothelial interactions and the transmigration of monocytes from the vasculature into extravascular tissues.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.81670035NSFC)the COPD Research Programs of Beijing Bethune Charitable Foundation(No.BJ-RW2020015J).
文摘Objective Cationic antimicrobial protein of 37 kDa(CAP37),a neutrophil-derived protein originally identified for its antimicrobial activity,is now known to have many regulatory effects on host cells.However,its role in the pathogenesis of chronic obstructive pulmonary disease(COPD)has not been studied.We therefore investigated the expression of CAP37 in COPD and its effects on airway structural cells,including bronchial epithelial cells,smooth muscle cells,and fibroblasts.Methods CAP37 was detected in the lung tissue,sputum,and plasma of COPD patients and the control subjects,as well as in the neutrophils stimulated by cigarette smoke extract(CSE).BEAS-2B cells,human bronchial smooth muscle cells(HBSMCs),and MRC-5 cells were treated with CAP37 or an anti-CAP37 antibody plus CAP37.Interleukin(IL)-6 and IL-8 were detected in the BEAS-2B cells.The cell proliferation was analyzed in the HBSMCs.Collagens were also detected in the MRC-5 cells.Results The expression of CAP37 was increased in the lung tissue and sputum supernatant of the COPD patients compared with the control subjects.The sputum supernatant CAP37 levels were inversely correlated with the forced expiratory volume in the first second percentage predicted in COPD.CAP37 was induced by CSE stimulation in the peripheral blood neutrophils from healthy non-smokers.CAP37 induced expression of IL-6 and IL-8 in BEAS-2B cells,and collagen expression of lung fibroblasts(MRC-5 cells).However,CAP37 did not significantly alter the proliferation of the HBSMCs.Conclusion Our findings indicated that neutrophil-derived CAP37 may be involved in airway inflammation and fibrosis in COPD via affecting the bronchial epithelial cells,and fibroblasts,thus suggesting a possible role of CAP37 in the development and progression of COPD.
基金supported in part by an Established Investigata Grant from the American Heart Association and Public Health Service Grant AI28018 from the Natianal Institute of Allergy and Infectious Diseases
文摘PURPOSE: To investigate the role of cationic antimicrobial protein of Mr 37 kDa (CAP37) a neutrophil-derived inflammatory mediator on endothelial cell function. DATA SOURCES: Endothelial cells used in this study were obtained from human lung microvessels and rat aorta. The latter was a kind gift of Dr. Paula Grammas. The mono-mac 6 cell line used in this study was the generous gift of Dr. H.W. Loms Ziegler-Heitbrock. STUDY SELECTION AND DATA EXTRACTION: Endothelial cell proteins kinase C activity was determined by measuring calcium- and phospholipid-dependent phosphorylation of histone. Endothelial cell migration was determined using Costar Transwell apparatus. Cell surface expression of adhesion molecules, ICAM-1 and PECAM-1 was determined using flow cytometry. RT-PCR was used to amplify the CAP37 from endothelial cells treated with LPS. RESULTS: We demonstrated that CAP37 which was originally identified as having potent antimicrobial activity and chemotactic activity for monocytes was capable of modulating endothelial cell functions. CAP37 activated endothelial cell protein kinase C in a dose- and time-dependent fashion. Importantly CAP37 increased the adhesive properties of the endothelium for monocytes. CAP37 upregulated the well known adhesion molecules, ICAM-1 and PECAM-1 in a dose- and time-dependent manner. In addition, CAP37 promoted endothelial cell migration. Further investigations indicated that CAP37 was induced in endothelial cells in response to pro-inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-1 alpha as well as inflammatory mediators such as lipopolysaccharide. Unstimulated endothelial cells did not constitutively express CAP37. The cDNA sequence of endothelial CAP37 was determined and found to be highly homologous to the sequence obtained for neutrophil-derived CAP37. CONCLUSIONS: Our studies strongly suggest that CAP37 plays a pivotal role in monocyte-endothelial interactions and the transmigration of monocytes from the vasculature into extravascular tissues.
