DEFECT OF FC-RECEPTORS AND PHENOTYPICAL CHANGES IN SINUSOIDAL ENDOTHELIAL-CELLS IN HUMAN LIVER-CIRRHOSIS

To analyze the pathological changes occurring in Fc receptors (FcRs) i n sinusoidal endothelial cells (SECs) in chronic liver diseases, we fi rst characterized immunohistochemically the SEC FcRs by using monoclon al antibodies (MAbs) to FcRs and then investigated the distribution of the SEC FcRs by using peroxidase-antiperoxidase IgG complexes as a li gand on frozen sections. MAb 2E1 to FcRII reacted with SECs in a simil ar manner to peroxidase-antiperoxidase IgG and blocked the peroxidase- antiperoxidase IgG binding to SECs, whereas MAbs 3G8 and Leu-11b to Fc RIII did not. FcRs in normal liver were found along the sinusoidal wal ls, except for those in the outer periportal zones, but FcRs in chroni c active hepatitis and cirrhosis were intermittently or focally absent . The lengths of the FcR-positive portion of sinusoids in unit areas w ere respectively about 54% and 76% of the normal values in active and inactive cirrhosis. Where FcRs were absent, the MAbs CD36, CD31, and E N4 revealed the presence of sinusoids and, in active cirrhosis, freque ntly the thickening of liver cell plates. The FcR-negative SECs in the outer periportal zones of normal livers were different from the SECs of other sites in the presence of PAL-E antigen and a rich amount of E N4 antigen, though these sinusoids possessed Kupffer cells and no peri sinusoidal deposition of laminim. The FcR-negative SECs in liver disea ses occasionally presented the character of ordinary blood vessels, vi z., PAL-E antigen, CD34 antigen, and a deficiency of Kupffer cells, re gardless of perisinusoidal laminin deposition. However, they preserved the character of normally FcR-possessing SECs, viz., CD36 antigen, an d a small amount of EN4 and CD31 antigens. These findings indicate tha t the outer-periportal SECs in normal livers are phenotypically differ ent from other SECs and that the SECs in diseased livers frequently un dergo phenotypical changes, including loss of FcRs, regardless of peri sinusoidal laminin deposition, i.e., capillarization of the sinusoids. These phenotypical changes in SECs may reduce the capacity of FcR-med iated IgG-IC metabolism in diseased liver.