Fibroblast stimulation in schistosomiasis. VII. Egg granulomas secrete factors that stimulate collagen and fibronectin synthesis

Tissue fibrosis in schistosomiasis is largely responsible for the important morbidity that results from infection with the trematode worms, Schistosoma. Neither the migrating larval forms (cercariae) nor the intravascular adult worms appear to incite pathological responses that are important in chronic schistosomiasis. On the other hand, eggs deposited in tissue incite chronic granulomatous inflammatory responses that are the hallmark of infection and precede the onset of adjacent tissue fibrosis. We previously reported that products of the egg granulomas can stimulate a number of relevant responses in fibroblast cultures that in vivo would be expected to promote tissue fibrosis. We report here that the granulomas secrete factors that in vitro can stimulate collagen and fibronectin synthesis in fibroblasts. We determined that activity stimulating collagen synthesis is congruent to 10 Kd (gel filtration) with a pI of congruent to 5.5 (isoelectric focusing); additional activity is also detected in some other fractions (congruent to Kd; pI approximately 7.0). In contrast, the activity stimulating fibronectin synthesis was congruent to 22 Kd with a pI of 5.5. Activity was also present in fractions of 50 Kd with pI of approximately 7.5. Fibroblasts grown in granuloma supernatant-containing medium contained greater steady-state levels of specific mRNA coding for type I procollagen and fibronectin compared with cells cultured in unsupplemented medium. These observations support the hypothesis that biologically active molecules secreted by granuloma cells are instrumental in the initiation of tissue fibrosis in schistosomiasis.