436 THE POSSIBLE ASSOCIATION BETWEEN FAS EXPRESSION IN PERIPHERAL BLOOD LEUKOCYTES, SERUM FAS AND FASL, AND HEPATIC INFLAMMATORY ACTIVITY IN CHRONIC HEPATITIS C

Abstract

Background and Aims: Fas/Fas ligand system is established as one of regulatory pathways of apoptosis. Fas receptor is type I membrane protein belonging to tumour necrosis factor receptor family that mediates apoptosis. Fas ligand (FasL) activates apoptosis by binding to Fas and inducing its oligomerization. Soluble Fas receptor (sFas) is considered as inhibitor of apoptosis, whereas soluble Fas ligand (sFas-L) seems to induce apoptosis in Fas-expressing cells. This study is an attempt to evaluate influence of hepatic inflammation and fibrosis in chronic hepatitis C (CHC) on the Fas expression in peripheral blood leukocytes (PBL) and serum concentration of sFas and sFasL. Methods: Eighty-one CHC patients were enrolled in the study. Histopathological evaluation of hepatic inflammatory activity and fibrosis and liver function blood tests were determined. Control group consisted of 14 healthy individuals. Subset determination and quantitation of CD4+, CD8+, CD19+, CD16+, CD14+ PBL and membranous Fas expression were performed by flow cytometry. Proportions of every PBL subset, percentage of cells stained for Fas receptor and its median intensity of fluorescence (MIF) were determined. Serum concentrations of sFas and sFas-L were measured by ELISA methods. Results: Significantly (P< 0.05) increased expression of Fas receptor in CD4+ and CD8+ PBL in CHC was observed. There were no significant differences in sFas and FasL serum concentration in CHC vs. healthy individuals. Expression of Fas receptor in CD4+ and CD14+ was significantly impacted by inflammatory activity (CD4+: n = 51, H = 8.06, P< 0.05; CD14+: n = 50, H = 8.53, P< 0.05) and fibrosis (CD4+: n = 51, H = 7.75, P = 0.05; CD14+: n = 50, H = 11.61, P< 0.01). The sFasL serum concentration was found to significantly increase in dependency on hepatic histopathological inflammatory activity (n = 71, H = 7.99, P< 0.05). Association between sFas serum concentration and histopathological markers of disease activity were not found. Although sFas serum concentration correlated with expression of Fas receptor in CD4+ (R= 0.31, P< 0.05). Conclusions: In our study we detected increased expression of Fas in T cells in CHC. Hepatic inflammatory activity seems to influence membranous expression of Fas receptor in PBL and serum concentration of sFasL. This might reflect the susceptibility of certain subsets of PBL to apoptosis in CHC.