AIM：To examine the expression of intercellular adhesion molecule-1 （ICAM-1） and lymphocyte function-associated antigen-1（LFA-1）expression on canals of Hering （COH）and bile ductules associated with the autoimmun...AIM：To examine the expression of intercellular adhesion molecule-1 （ICAM-1） and lymphocyte function-associated antigen-1（LFA-1）expression on canals of Hering （COH）and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis（PBC）．METHODS：Ten wedged liver biopsies of PBC（five cases each of stages 2 and 3）were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse mAbs.In situ hybridization was done to examine the messenger RNA expression of ICAM-1 in formalin-fixed．paraffin-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification （CSA）technique．Immunogold-silver staining for electron microscopy was Derrormed using anti-ICAM and anti-LFA-1 mouse mAbs．The immunogold particles on epithelial cells of bileductules and cholangiocytes of CoH cells were counted and analyzed semi-quantitatively．Western blotting was performed to confirm ICAM-1 protein expression．RESULTS：In liver tissues of PBC patients．immunohi-stochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules，and also on mature cholangiocytes but not on hepatocytes in CoH．LFA-1-positive lymphocytes were closely associated with epithelial cells in bile ductules．ICAM-1 expression at protein level was confirmed by Western blot．In situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the bileductules．By immunoelectron microscopy，ICAM-1 was demonstrated on the basal suface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged COH．Cells with intermediate morphology resembling progenitor cells in Coil were not labeled with ICAM-1 and LFA-1．CONCLUSION：De novo expression of ICAM-1 both on mature cholangiocytes in COH and epithelial cells in bile ductules in PBC implies that lymphocyte-induced destruction through adhesion by ICAM-1 and binding of LFA-1-expressing activated lymphocytes takes place not only in bile ductules but also in the COH．展开更多
AIM: An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins ar...AIM: An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes including cholesterol transport. This study aims to examine the role of caveolin in PBC.METHODS: Immunohistochemical and Western blottingstudies were performed on human liver specimens obtained from patients with PBC and normal liver samples. The expression of caveolin (CAV)-1 and -2 was determined using specific antibodies.RESULTS: In normal liver, scanty immunostaining for CAV1 and -2 was observed in bile ductules. In PBC liver samples, the expression levels of CAV-1 and -2 were increased on proliferating bile ductules especially in stage 3 cases, but was sparse on interlobular bile duct in stage 1 specimens. Especially, the regenerating bile ductules at the interface of portal tracts and necrotic areas were immunostained intensely for CAV-1 and -2. These phenomena were confirmed by Western blot.CONCLUSION: The present results demonstrate increased expression of caveolins in proliferating bile ductules in PBC, which may be related to the homeostasis of cholesterol transport in regenerating bile ductules in PBC liver.展开更多
文摘AIM：To examine the expression of intercellular adhesion molecule-1 （ICAM-1） and lymphocyte function-associated antigen-1（LFA-1）expression on canals of Hering （COH）and bile ductules associated with the autoimmune process of bile duct destruction in primary biliary cirrhosis（PBC）．METHODS：Ten wedged liver biopsies of PBC（five cases each of stages 2 and 3）were studied. The liver specimens were processed for transmission electron microscopy. Immunohistochemistry was performed using anti-ICAM-1 and anti-LFA-1 mouse mAbs.In situ hybridization was done to examine the messenger RNA expression of ICAM-1 in formalin-fixed．paraffin-embedded sections using peptide nucleic acid probes and the catalyzed signal amplification （CSA）technique．Immunogold-silver staining for electron microscopy was Derrormed using anti-ICAM and anti-LFA-1 mouse mAbs．The immunogold particles on epithelial cells of bileductules and cholangiocytes of CoH cells were counted and analyzed semi-quantitatively．Western blotting was performed to confirm ICAM-1 protein expression．RESULTS：In liver tissues of PBC patients．immunohi-stochemistry showed aberrant ICAM-1 expression on the plasma membrane of epithelial cells lining bile ductules，and also on mature cholangiocytes but not on hepatocytes in CoH．LFA-1-positive lymphocytes were closely associated with epithelial cells in bile ductules．ICAM-1 expression at protein level was confirmed by Western blot．In situ hybridization demonstrated ICAM-1 mRNA expression in bile ductules and LFA-1 mRNA in lymphocytes infiltrating the bileductules．By immunoelectron microscopy，ICAM-1 was demonstrated on the basal suface of epithelial cells in bile ductules and on the luminal surfaces of cholangiocytes in damaged COH．Cells with intermediate morphology resembling progenitor cells in Coil were not labeled with ICAM-1 and LFA-1．CONCLUSION：De novo expression of ICAM-1 both on mature cholangiocytes in COH and epithelial cells in bile ductules in PBC implies that lymphocyte-induced destruction through adhesion by ICAM-1 and binding of LFA-1-expressing activated lymphocytes takes place not only in bile ductules but also in the COH．
文摘AIM: An increase in bile ductular structures is observed in diverse human liver diseases, especially in primary biliary cirrhosis (PBC). These structures harbor the progenitor cell component of the liver. Caveolins are cholesterol-binding proteins involved in the regulation of several intracellular processes including cholesterol transport. This study aims to examine the role of caveolin in PBC.METHODS: Immunohistochemical and Western blottingstudies were performed on human liver specimens obtained from patients with PBC and normal liver samples. The expression of caveolin (CAV)-1 and -2 was determined using specific antibodies.RESULTS: In normal liver, scanty immunostaining for CAV1 and -2 was observed in bile ductules. In PBC liver samples, the expression levels of CAV-1 and -2 were increased on proliferating bile ductules especially in stage 3 cases, but was sparse on interlobular bile duct in stage 1 specimens. Especially, the regenerating bile ductules at the interface of portal tracts and necrotic areas were immunostained intensely for CAV-1 and -2. These phenomena were confirmed by Western blot.CONCLUSION: The present results demonstrate increased expression of caveolins in proliferating bile ductules in PBC, which may be related to the homeostasis of cholesterol transport in regenerating bile ductules in PBC liver.
