Fibroblast stimulation in schistosomiasis. IX. Schistosomal egg granulomas from congenitally athymic mice are deficient in production of fibrogenic factors.
Schistosomal egg granulomas spontaneously secrete fibrogenic factors, suggesting that there exists a molecular link between granulomatous inflammation and hepatic fibrosis in schistosomiasis. To further assess this possibility, we compared elaboration of fibrogenic factors by egg granulomas isolated from Schistosoma mansoni-infected euthymic mice that develop substantial liver fibrosis, with those elaborated by similarly infected congenitally athymic mice that develop minimal fibrosis. Conditioned medium from cultures of granulomas from euthymic mice stimulated fibroblast proliferation, chemotaxis, and synthesis of collagen, collagenase, tissue inhibitor of metalloproteinases, and hyaluronate, whereas those prepared from cultures of granulomas isolated from athymic mice were relatively or absolutely deficient in such activities. These observations provide a correlation between the presence of fibrosis in vivo and the production of fibrogenic factors and reinforce our hypothesis that granuloma-derived fibrogenic factors play a role in the pathogenesis of liver fibrosis in schistosomiasis. Furthermore, the results of this study suggest a central role of T lymphocytes in the fibrogenic process.
Prakash
S
S
Division of Geographic Medicine and Infectious Diseases, New England Medical Center Hospitals, Boston, MA.
Postlethwaite
A E
AE
Stricklin
G P
GP
Wyler
D J
DJ
D000818:Animals; D002455:Cell Division; D002633:Chemotaxis; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology; D006023:Glycoproteins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D003012:Microbial Collagenase / Q000378:metabolism; D010063:Ovum; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D006025:Glycosaminoglycans; D019714:Tissue Inhibitor of Metalloproteinases; D003012:Microbial Collagenase