Basic and Clinical Studies on the Mechanism of Liver Cell Necrosis in Hepatits Type B

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(1)Purification and Analysis of Hepatocyte Receptor for Polymerized Human Serum Albumin : Supernatant of homogenate from the normal human liver was separated by SDS-PAGE and transferred to nitrocellulose membrane. The transferred proteins were reacted with polymerized human serum albumin(pHSA)labeled with horseradish peroxidase and two bands with molecular weight of 15 kD and 14.8 kD were detected. The two proteins were hepatocyte receptors for pHSA(hepatocyte-pAR). Immunofluorescence microscopy using antibody to hepatocyte-pAR revealed hepatocyte-pAR was localized in cytoplasm and cell membrane of normal human hepatocytes.(2)Clinical Significance of Serum Hepatocyte-pAR and Antibody to Hepatocyte-pAR in Patients with Liver Diseases : Purified hepatocyte-pAR was coated on a microplate and serum antibody to hepatocyte-pAR was detected by ELISA. All sera from normal subjects were negative for antibody to hepatocyte-pAR. In patients with positive HBsAg. 56 % in HBeAg positive patients and … More 58 % in HBeAb-positive patients were positive for the antibody. Patients with positive HBsAb. especially with positive anti-liver membrane antibody, showed high frequency in hepatocyte-pAR antibody. Hepatocyte-pAR was detected in sera of some patients with positive HBeAg, suggesting the intimate relationship with liver cell injury.(3)Fate of Polymerized Human Serum Albumin(pHSA)in vivo : pHSA was conjugated with colloidal gold and injected into the portal vein of rats. Human liver biopsy specimen was also perfused with colloidal gold conjugated with pHSA. Colloidal gold particles were taken up by sinusoidal endothelial cells and Kupffer cells through coated pits and vesicles. Further studies are needed to elucidate the interaction between pHSA and human hepatocytes.(4)Significance of Adhesion Molecules in Liver Cell Necrosis : Adhesion molecules such as lymphocyte associate antigen-1(LFA-1)and intercellular adhesion molecules-1(ICAM-1)were examined in biopsy specimens from patients with chronic hepatitis type B. LFA-1 was expressed on lymphocytes infiltrating into the area such as piecemeal necrosis and focal necrosis. In such area, ICAM-1 was expressed on liver cell membrane in association with HLA class 1 antigen. These results suggest that adhesion molecule may play an important role in the process of liver cell necrosis. Less