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.