Changes of sinusoidal basement membrane collagens in early hepatic fibrosis induced with CCl4 in cynomolgus monkeys

CCl4 was chronically administrated for 25 months to induce hepatic fibrosis in three cynomolgus monkeys so as to examine the alteration of basement membrane-related collagens during the liver injury. Although type IV collagen was immunohistochemically present along sinusoidal walls before and during the CCl4 administration, basement membrane-associated collagen (BAC), which was recognized with JK-132 monoclonal antibody, appeared around sinusoids at five to ten months of CCl4 administration. We previously developed a sandwich enzyme linked-immunosorbent assay, utilizing two monoclonal antibodies, anti-BAC antibody (JK-132) and anti-type IV collagen antibody (JK-199) [Int Hepatology Commun 1995; 4: 1-8]. The serum level of the collagen complex, which is disulfide-bridged with BAC and type IV collagen, was simultaneously monitored. The serum level of the complex at the initial stage of the examination was 19-34 ng/ml and gradually increased in relation to the intensity of immunofluorescence of BAC and type IV collagen in sinusoids and connective tissues, up to 51-57 ng/ml. The serum collagen complex levels showed a weak correlation with serum hyaluronic acid, a serum marker of hepatic fibrosis. The serum GOT, GPT, ALP and CHE levels did not reflect the alteration of sinusoids or relate to the serum collagen complex level. The increase in BAC around sinusoids and the increase of collagen complex with BAC and type IV collagen in the sera, correlate with early lesional events in hepatic fibrosis.