chondroitin-sulfates and Liver-Diseases--Parasitic

An important pathological outcome of schistosomiasis is hepatic fibrosis, with a significant deposit of collagens and proteoglycans. In this study, hepatic and granuloma-associated glycosaminoglycans (GAGs) were 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 the 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 granulomatous GAGs--mainly chondroitin sulfates A/C and B--represented only one sixth of total GAGs amount. Therefore, the increase was found predominantly in the parenchyma. In this compartment, qualitative changes were also induced with a marked increase in the proportion of chondroitin sulfates A/C balanced by a decrease in the proportion of heparan sulfate 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 in this compartment. By contrast, IFN gamma had neither quantitative nor qualitative effect on fibroinflammatory granulomas. In these structures, the absence of heparan sulfate--which is suspected to mediate IFN gamma activity--might explain these observations.

Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Extracellular Matrix; Female; Glycosaminoglycans; Granuloma; Heparitin Sulfate; Interferon-gamma; Liver; Liver Diseases, Parasitic; Mice; Schistosomiasis mansoni

Proteoglycans synthesized in vitro by periovular granulomas isolated from livers of schistosome-infected mice were compared with those produced by granuloma-derived cell lines: the primary cell line GR and the permanent cell line GRX. Proteoglycans were metabolically labelled with 35S-sulfate and extracted with 4 M guanidine-HCl containing 2.0% Triton X-100, in the presence of proteinase inhibitors. The radiolabelled proteoglycans were purified and characterized by anion-exchange, gel-filtration and affinity-column chromatography. Heparan sulfate proteoglycans (HS-PGs) and chondroitin sulfate/dermatan sulfate-containing proteoglycans (CS/DS-PGs) were detected in both the culture medium and the cell-associated fractions obtained from GR cells. More than 90% of the cell-associated HS-PG from these cells contained a hydrophobic portion, as evidenced by their ability to bind to octyl-Sepharose. In contrast, among the secreted proteoglycans, it was the CS/DS-PG and not the HS-PG that bound to this resin. The major fractions of cell-associated and secreted proteoglycans from GRX cells were HS-PGs. Similar to HS-PGs from GR cells, 50% of the cell-associated HS-PG bound to octyl-Sepharose, while only 20% of secreted proteoglycans (HS-PGs) bound to this resin. The proteoglycans purified from the whole granuloma were composed mainly of DS-PG, of a size and hydrophobicity similar to the CS/DS-PG from GR cells. Possible correlations among the structure, secretion, distribution and function of proteoglycans in granulomatous reactions are discussed.

Topics: Animals; Cell Line; Chondroitin Sulfates; Chromatography, Affinity; Chromatography, Gel; Chromatography, Ion Exchange; Connective Tissue; Dermatan Sulfate; Female; Granuloma; Heparitin Sulfate; Liver Diseases, Parasitic; Male; Mice; Mice, Inbred C3H; Proteoglycans; Schistosomiasis mansoni

Sulphated glycosaminoglycans were isolated from schistosome-induced hepatic granuloma and from the pericellular, intracellular and extracellular compartments of two murine cell lines derived from granulomas: the primary cell line GR, and the permanent cell line GRX, established spontaneously from GR. The glycosaminoglycans composition in the whole granuloma was similar to that observed in the intracellular and extracellular compartments of GR cells. This result suggests that GR cells may be the major cell population involved in the synthesis and accumulation of glycosaminoglycans in the granulomas, and play an important role in the process of hepatic fibrosis. The conversion of the primary cell line GR into the established GRX cells did not modify the ratios that prevail among different glycosaminoglycans of the cell surface. However, it decreased the synthesis and secretion of glycosaminoglycans, reduced the proportion of iduronic acid units in the chondroitin sulphate, and increased the proportion of heparan sulphate in intracellular and extracellular pools. These characteristics of the GRX cells are similar to those observed in long-term cultures of smooth-muscle cells. In agreement with the general phenomenon of progressive de-differentiation during in-vitro culture of primary cell lines, these data indicate that the connective tissue cells of liver may belong to the myofibroblastic cell lineage.

Topics: Animals; Cell Line; Chondroitin Sulfates; Female; Glycosaminoglycans; Granuloma; Heparitin Sulfate; Liver Diseases, Parasitic; Male; Mice; Mice, Inbred C3H; Schistosomiasis mansoni