Fibroblast stimulation in schistosomiasis. II. Functional and biochemical characteristics of egg granuloma-derived fibroblast-stimulating factor.

The pathogenetic mechanisms that underlie hepatic fibrosis in schistosomiasis are unknown, but may be under the regulation of molecules secreted by the hepatic granulomas that encase the helminth eggs. Previous studies in mice demonstrated that isolated Schistosoma mansoni egg granulomas can elaborate in vitro substances that stimulate fibroblast proliferation and collagen synthesis. The present study provides the initial characterization of the granuloma-derived factor(s). Serum-free cell culture supernatants from isolated granulomas contained activity that stimulated the uptake of (3H)-thymidine by quiescent human dermal fibroblasts. This activity was present in fractions (Sephadex G-200 chromatography) with estimated m.w. of 30,000 to 40,000. Activity eluted with linear salt gradients from ion exchange columns (DEAE Sephadex) with 0.4 to 0.7 and 1.5 to 1.8 M NaCl (pH 8.4). Activity was present in fractions with approximate pI of 6 to 6.5 and 4, prepared by flat-bed isoelectrofocusing of crude supernatant in granular gel. Activity that stimulated thymocyte proliferation in an interleukin 1 (IL 1) assay was present in crude granuloma supernatants as well as in the partially purified fractions that contained fibroblast-stimulating activity. We conclude that the granuloma-derived fibroblast-stimulating factor has biologic activity similar to IL 1 but on the basis of m.w. and pI determination is distinct from IL 1.