BACKGROUND/AIMS: Complement activation is one of the mechanisms involved in inflammatory lesions. Initiation of the complement terminal pathway at a cell surface leads to the formation of a cytolytic membrane attack complex. Our study assess whether a membrane attack complex-associated mechanism is involved in liver cell necrosis of fulminant and subfulminant hepatitis. METHODS: Immunostaining for membrane attack complex was compared with immunostaining for cytokeratin and complement inhibitory proteins such as membrane cofactor protein, decay-accelerating factor, and homologous restriction factor in 15 patients with fulminant hepatitis and 5 patients with nonfulminant acute hepatitis. RESULTS: In all patients, hepatocytes surrounding necrotic areas, but not those at a distance, were stained for membrane attack complex, whereas the opposite staining pattern for membrane cofactor protein was observed. In controls, no hepatocyte staining for membrane attack complex was observed, whereas membrane cofactor protein, but not decay-accelerating factor or homologous restriction factor, was detected on hepatocytes. CONCLUSIONS: Complement activation by antibody-dependent or non-antibody-dependent mechanisms might be involved in the pathogenesis of either fulminant or acute hepatitis. Modulation of membrane cofactor protein expression on hepatocytes might contribute to the sensitivity of hepatocytes to membrane attack complex and subsequent cell lysis.
BACKGROUND/AIMS: Complement activation is one of the mechanisms involved in inflammatory lesions. Initiation of the complement terminal pathway at a cell surface leads to the formation of a cytolytic membrane attack complex. Our study assess whether a membrane attack complex-associated mechanism is involved in liver cell necrosis of fulminant and subfulminant hepatitis. METHODS: Immunostaining for membrane attack complex was compared with immunostaining for cytokeratin and complement inhibitory proteins such as membrane cofactor protein, decay-accelerating factor, and homologous restriction factor in 15 patients with fulminant hepatitis and 5 patients with nonfulminant acute hepatitis. RESULTS: In all patients, hepatocytes surrounding necrotic areas, but not those at a distance, were stained for membrane attack complex, whereas the opposite staining pattern for membrane cofactor protein was observed. In controls, no hepatocyte staining for membrane attack complex was observed, whereas membrane cofactor protein, but not decay-accelerating factor or homologous restriction factor, was detected on hepatocytes. CONCLUSIONS: Complement activation by antibody-dependent or non-antibody-dependent mechanisms might be involved in the pathogenesis of either fulminant or acute hepatitis. Modulation of membrane cofactor protein expression on hepatocytes might contribute to the sensitivity of hepatocytes to membrane attack complex and subsequent cell lysis.
Authors: Filip M Segers; Froukje J Verdam; Charlotte de Jonge; Bas Boonen; Ann Driessen; Ronit Shiri-Sverdlov; Nicole D Bouvy; Jan Willem M Greve; Wim A Buurman; Sander S Rensen Journal: PLoS One Date: 2014-10-09 Impact factor: 3.240