DISTRIBUTION OF HEPATIC GLYCOSAMINOGLYCANS DURING ACUTE SCHISTOSOMIASIS - MODULATION BY IFN-GAMMA TREATMENT

An important pathological outcome of schistosomiasis is hepatic fibros is, with a significant deposit of collagens and proteoglycans. In this study, hepatic and granuloma-associated glycosaminoglycans (GAGs) wer e analyzed both quantitatively and qualitatively at the acute stage of murine infection with Schistosoma mansoni. The effects of IFN gamma, which has been successfully used for reducing collagen deposition in t he liver during schistosomiasis, were also analyzed in granulomas and the surrounding liver parenchyma. Acute schistosomiasis resulted in a 4.4-fold increase in total hepatic GAG content, from which granulomato us GAGs - mainly chondroitin sulfates A/C and B - represented only one sixth of total GAGs amount. Therefore, the increase was found predomi nantly in the parenchyma. Tn this compartment, qualitative changes wer e also induced with a marked increase in the proportion of chondroitin sulfates A/C balanced by a decrease in the proportion of heparan sulf ate and dermatan sulfate. IFN gamma reduced parenchymal GAG content by 47%. Qualitatively, the cytokine increased the proportion of heparan sulfate and reduced the quantity of chondroitin sulfates A/C by half i n this compartment. By contrast, IFN gamma had neither quantitative no r qualitative effect on fibroinflammatory granulomas. In these structu res, the absence of heparan sulfate - which is suspected to mediate IF N gamma activity- might explain these observations.