Hepatic fibrosis is the major clinical sequela of infection with the helminth Schistosoma mansoni. However, little is known regarding its dynamics and regulation in schistosomiasis. The present study presents the dynamics of deposition and resorption of two major extracellular matrix components of fibrosis, glycosaminoglycans and collagens, during the course of experimental S. mansoni infection. Early in infection (6 weeks), glycosaminoglycan biosynthesis was markedly elevated, as was collagen biosynthesis. This led to significant accumulations of these two molecules at a glycosaminoglycan/collagen ratio similar to that observed in livers of uninfected mice (uronic acid/hydroxyproline ratio of 1.10 at 6 weeks compared to normal value of 1.25). During maximal hepatic fibrosis (12 to 18 weeks), both collagen and glycosaminoglycan biosynthesis continued to increase but the extracellular matrix shifted to a lower glycosaminoglycan/collagen ratio of 0.42, suggesting enhanced glycosaminoglycan breakdown. In addition, during this acute stage of infection, Type I collagen was the predominant isotype synthesized, whereas total collagenolytic activity degrading Type I collagen was maximal. During chronic infection, a decrease in the content of both hepatic glycosaminoglycans and collagens were noted, with a glycosaminoglycan/collagen ratio of 0.63. Decreased glycosaminoglycan content paralleled diminished biosynthetic rates. On the other hand, an over 50% reduction in collagen content (from 18 to 24 weeks) appeared not to result from diminished biosynthesis but from a switch in the predominant collagen isotype synthesized (from Type I to Type III), matched by an enhanced constitutive collagenolytic activity directed toward this type of collagen.(ABSTRACT TRUNCATED AT 250 WORDS)

The present study investigates the immunoregulation of hepatic fibrosis in experimental murine schistosomiasis. Disease parameters measured were portal pressure, hepatic granuloma area, hepatic interstitial collagen, and glycosaminoglycans. C57BL/6 mice were infected with 25 Schistosoma mansoni cercariae and administered splenocytes or serum derived from uninfected mice or chronically infect syngeneic mice at 6 and 7 wk of infection. Immunologically mediated modulation was noted in animals receiving splenocytes derived from chronically infected mice. Both a reduction in portal pressure and hepatic granuloma areas were noted. Hepatic collagen content but not glycosaminoglycan content was reduced by the administration of either lymphoid cells or serum from chronically infected mice. The isotypic profile of hepatic interstitial collagens was modulated by both the administration of serum or lymphoid cells. Augmented levels of type III collagen was noted on administration of serum derived from chronically infected mice, whereas type I collagen levels were relatively elevated on administration of splenocytes. The data indicate that immunomodulation of inflammation and hepatic fibrosis can occur in murine schistosomiasis but that fibrotic events and inflammatory processes are independently modulated.

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