Effect of chemotherapy on hepatic collagen and glycosaminoglycan metabolism in Schistosoma mansoni-infected mice.
The dynamics of biosynthesis and accumulation of collagenous proteins and glycosaminoglycans (GAGs) in liver granulomas induced by eggs of Schistosoma mansoni were studied in mice following eradication of adult worms by chemotherapy. The relatively synchronous granulomas around parasite eggs were isolated from the livers at ensuing 2-week intervals; the number of recoverable granulomas per liver gradually decreased and was 7% of initial values at 20 weeks. Hepatic or granuloma-associated extracellular matrix components increased for 4 weeks after treatment despite cessation of ova deposition. At 12 weeks after chemotherapy the rate of GAG biosynthesis per total liver granuloma fraction, measured by 3H-glucosamine incorporation, decreased dramatically; this was followed by a decrease in the amount of GAGs present. The rate of collagen biosynthesis per total liver granuloma fraction, measured by 3H-proline incorporation, began to decline at 14 weeks and a decrease in the amount of collagen present was noted at 16 weeks. Our results demonstrated that liver granulomas induced by S. mansoni eggs synthesize collagens and GAGs for about 4-6 weeks following parasitological cure. The subsequent resolution of granulomas proceeds first by a reduction in GAG biosynthesis followed 4-8 weeks later by decreased collagen biosynthesis, followed by accelerated resolution of both collagen and GAGs.
Schiltz
J R
JR
Department of Medicine, Case Western Reserve University, Cleveland, OH.
Olds
G R
GR
Kresina
T F
TF
Mahmoud
A A
AA
D000818:Animals; D003094:Collagen / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006099:Granuloma / Q000378:metabolism; D006826:Hycanthone / Q000627:therapeutic use; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000378:metabolism*; D013997:Time Factors
D006025:Glycosaminoglycans; D006826:Hycanthone; D003094:Collagen