Fibroblast stimulation in schistosomiasis. XI. Purification to apparent homogeneity of fibroblast-stimulating factor-1, an acidic heparin-binding growth factor produced by schistosomal egg granulomas.

Abstract

Liver fibrosis is the most serious complication of infection with Schistosoma mansoni and Schistosoma japonicum and is responsible for severe morbidity and mortality in hundreds of thousands of patients in many Third World nations. The pathogenesis of this condition remains to be elucidated. We proposed that certain cytokines produced by cells that comprise the chronic granulomas that surround the helminth eggs within the liver initiate hepatic fibrogenesis. We now report our successful purification to apparent homogeneity of the egg granuloma-derived fibroblast mitogen. The high affinity of this factor for heparin (elutes from heparin-Sepharose with 1.5 M NaCl) facilitates its purification by a two-step procedure, and identifies the cytokine as a heparin-binding growth factor (HBGF). Furthermore, because it has an isoelectric point approximately equal to 6.2, it has one of the characteristics of a class 1 (acidic) HBGF. We immunized rabbits with the purified factor and observed that the resulting antibodies (IgG) detected the factor but not acidic fibroblast growth factor (the prototypic class 1 HBGF) either by dot-blot ELISA or neutralization of biologic activity. The granuloma product and fibroblast growth factor also differ in target-cell specificity and amino acid composition. On the basis of these distinctions, we have designated the granuloma-derived mitogen fibroblast-stimulating factor-1. With the availability of purified fibroblast-stimulating factor-1 and the future analysis of its amino acid sequence, its structural relationship to other mesenchymal growth factors can be determined.