Expression of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 protein and messenger RNA in primary biliary cirrhosis.

Objective Thisstudyexamined the role of intercellular adhesionmolecule-1 (ICAM-1) andlymphocyte function-associated antigen-1 (LFA-1) in the autoimmune process ofbileductdestruction intheearlystages ofprimary biliarycirrhosis (PBC). Materials and Methods TenPBC liver samplesand five controlsamples werestudied.Immunohistochemical studies of ICAM-1 and LFA-1,andWesternblot of ICAM-1 wereperformed.Immunoelectron microscopy was conducted using immunoglobulin-goldand silver staining. Human ICAM-land LFA-1 peptidenucleic acid probeswere usedfor in situ hybridization. ResultsIn PBC liver samples, immunohistochemistry showed aberrant ICAM-1 expression onbile ductepithelial plasma membrane andalsoluminal sites of endothelial plasma membraneof terminal portal venules. Westernblot confirmedICAM-1protein expression. LFA-1-positive lymphocytes wereassociatedwithepithelial cells of septalandinterlobularbile ducts.Immunoelectron microscopy localized ICAM-1 on the luminal and basal surfaces as well as on lymphocytesaround damaged bile ductepithelialcells, andLFA-1 onlymphocytes arounddamaged bile ducts. Messenger RNA expressionof ICAM-1 wasdemonstrated in bile ducts,and LFA-1 in lymphocytes around bile ducts. Conclusion Denovoexpressionof ICAM-1 and LFA1 at proteinandmRNA levels in PBC may implyan inductiverole of ICAM-1 throughbindingwithits ligand LFA-1 in the extravasationof activatedlymphocytes and lymphocyte-mediated bile ductdestruction. (Internal Medicine 42: 947-954, 2003)