Transforming growth factor-beta, basement membrane components and heparan sulphate proteoglycans in experimental hepatic schistosomiasis mansoni.

In an attempt to elucidate further the immunopathological pathways that underlie fibrogenesis induced by Schistosoma mansoni, we have studied the distribution of basement membrane compounds, heparan sulphate proteoglycans (HSPG) and the fibrogenic cytokine transforming growth factor (TGF)-beta in two models of experimental schistosomiasis mansoni (experimental murine infection and synchronous granulomas induced by injection of egg-antigen-coupled beads into the caecal vein). Deposition of the basement membrane proteins type IV collagen, laminin and entactin in schistosomal granulomas was seen 3 days after the implantation of egg-antigen-coupled beads in the liver and persisted over time (32 days). Up-regulation of the membrane-bound HSPG syndecan-1 was observed in the schistosomal granuloma. These syndecan-1-immunoreactive cells represented a distinct subpopulation of granuloma cells; they were different from both mature, unstimulated B-cells (CD40-positive) and endothelial cells (CD105-positive). Deposition of the matrix HSPG perlecan within the granuloma was most prominent 8-16 days after injection. TGF-beta expression was observed in acute (8 weeks) and chronically (13 weeks) infected mice, mainly at the periphery of the schistosomal granuloma and on Kupffer cells in the liver parenchyma. From these observations, we infer that schistosomal fibrosis is composed of various groups of matrix components and that TGF-beta, which is secreted by granuloma cells, is one of the fibrogenic mediators in schistosomal fibrogenesis.