Type I and type III procollagen peptides during hepatic fibrogenesis. An immunohistochemical and ELISA serum study in the CCl4 rat model.

Serum assays of procollagen peptides have been suggested as useful clinical indicators of hepatic fibrogenesis. To evaluate these assays in an experimental situation, the carbon tetrachloride model of hepatic fibrosis was produced in the rat. With affinity-purified antibodies, ELISA assays were developed and used for detecting nanogram quantities of the aminopropeptides of Types I and III procollagen (pro-I and pro-III) in rat serum. Serum SGPT levels were also determined. Routine histologic staining, as well as immunofluorescent staining for localization of Types I, III, and IV collagen and the aminopropeptides of Types I and III procollagen were performed on corresponding livers. It was found that serum pro-III levels were elevated after 45 and 70 days of treatment (28 +/- 15.2 ng/ml and 21 +/- 3.4 ng/ml, respectively) but returned to normal levels after 90 days of treatment (less than 3 ng/ml). Serum pro-I levels were elevated after 45 days of treatment (1028 +/- 504 ng/ml) but were normal at 70 and 90 days of treatment. Serum SGPT values were elevated at 45 and 70 days of treatment but were normal at 90 days of treatment. The decline in serum pro-III levels appeared to parallel the noted decline in SGPT values. Linear regression analysis revealed a good correlation between pro-III levels and histologic inflammation (r = 0.886) but a poor correlation between pro-III levels and histologic fibrosis (r = 0.116). Immunohistochemistry revealed that the pro-III antigen persists extracellularly for at least 45 days. Therefore, serum assays of pro-III might reflect extracellular collagen degradation as well as active collagen secretion. This would limit the clinical utility of the pro-III assay as an unequivocal marker of active hepatic collagen deposition.