chondroitin-sulfates and Intestinal-Diseases--Parasitic

Topics: Chondroitin Sulfates; Host-Parasite Interactions; Interleukin-18; Interleukin-2; Intestinal Diseases, Parasitic; Intestinal Mucosa; Mast Cells; Nematode Infections; Th2 Cells

The proteoglycan structure of mucosal mast cells (MMC) of the two species has been analyzed with histochemical in situ techniques. The findings indicate that human MMC, like human mast cells of several other sites, contain a heparin proteoglycan, unlike rat MMC which lack heparin but contain an oversulphated chondroitin sulphate. However, the dye-binding of the human MMC proteoglycan, like that of the rat, is highly susceptible to blocking by formaldehyde. Human MMC also exhibit a lower critical electrolyte concentration (CEC) of dye-binding than mast cells of other connective tissue sites, suggesting a relatively lower charge density and/or molecular weight of the glycosaminoglycan of the MMC. These findings thus suggest that the human MMC like those of the rat have a distinctive proteoglycan structure. Recent findings of another group indicate that the human MMC like those of the rat have also a distinctive proteinase composition. Finally, the mast cell response of the nasal mucosa during birch pollen allergy shows fundamental similarities to the nematode response of the rat intestinal mucosa. During both conditions mast cells are redistributed from the lamina propria into the epithelium, probably as a result of migration of mast cells or mast cell precursors. Taken together, these findings suggest the existence of a distinctive MMC phenotype also in man.

Topics: Animals; Chondroitin; Chondroitin Sulfates; Cystitis; Heparin; Humans; Intestinal Diseases, Parasitic; Mast Cells; Mucous Membrane; Organ Specificity; Peptide Hydrolases; Phenotype; Proteoglycans; Rats; Rhinitis, Allergic, Seasonal; Species Specificity; Staining and Labeling

Mucosal mast cell-derived chondroitin sulphates (sulphated proteoglycans) were assayed in gut washings and homogenate of FcRgamma-knockout (KO) and wild-type (WT) C57BL/6 mice challenged with Strongyloides venezuelensis in order to assess their possible role in secondary immunity against enteric nematodes. Groups of immune KO and WT mice were challenged by oral gavage with 300 infective larvae (L3). Establishment of infection was assessed by daily faecal analysis to determine the number of eggs per gram of faeces (EPG) and by adult worm recovery on days 5 and 13 post challenge. Mucosal mast cell (MMC) counts were done on days 5 and 13 post challenge while MMC-derived chondroitin sulphates in gut washings (days 1 and 5) and homogenate (day 8) were assayed by high performance liquid chromatography (HPLC). Results showed that patent infection occurred in challenged KO but not WT mice despite significantly higher mastocytosis in jejunal sections of KO than WT mice (p<0.001). Similarly but against prediction, significantly higher concentration of MMC-derived chondroitin sulphates was observed in gut homogenate of KO than WT mice (p<0.05). In contrast, significantly higher concentration of chondroitin sulphates was observed in gut washings of WT than KO mice (p<0.05). These results suggest that MMC in KO mice failed to release sufficient amount of sulphated proteoglycans into the gut lumen as did the WT mice, which may have been part of the hostile environment that prevented the establishment in and eventual expulsion of adult S. venezuelensis from the gut of WT mice following challenge.

Topics: Animals; Cell Count; Chondroitin Sulfates; Chymases; Feces; Intestinal Diseases, Parasitic; Intestinal Mucosa; Jejunum; Male; Mast Cells; Mice; Mice, Inbred C57BL; Mice, Knockout; Parasite Egg Count; Receptors, IgG; Serine Endopeptidases; Specific Pathogen-Free Organisms; Strongyloides; Strongyloidiasis

We examined effects of mast cell glycosaminoglycans on the establishment of the intestinal nematode, Strongyloides venezuelensis, in the mouse small intestine. When intestinal mastocytosis occurred, surgically implanted adult worms could not invade and establish in the intestinal mucosa. In mast cell-deficient W/Wv mice, inhibition of adult worm invasion was not evident as compared with littermate +/+ control mice. Mucosal mastocytosis and inhibition of S. venezuelensis adult worm mucosal invasion was tightly correlated. To determine effector molecules for the invasion inhibition, adult worms were implanted with various sulfated carbohydrates including mast cell glycosaminoglycans. Among sulfated carbohydrates tested, chondroitin sulfate (ChS)-A, ChS-E, heparin, and dextran sulfate inhibited invasion of adult worms into intestinal mucosa in vivo. No significant inhibition was observed with ChS-C, desulfated chondroitin, and dextran. ChS-E, heparin, and dextran sulfate inhibited adhesion of S. venezuelensis adult worms to plastic surfaces in vitro. Furthermore, binding of intestinal epithelial cells to adhesion substances of S. venezuelensis, which have been implicated in mucosal invasion, was inhibited by ChS-E, heparin, and dextran sulfate. Because adult worms of S. venezuelensis were actively moving in the intestinal mucosa, probably exiting and reentering during infection, the possible expulsion mechanism for S. venezuelensis is inhibition by mast cell glycosaminoglycans of attachment and subsequent invasion of adult worms into intestinal epithelium.

Topics: Animals; Caco-2 Cells; Carbohydrate Metabolism; Carbohydrates; Chondroitin Sulfates; Duodenum; Glycosaminoglycans; Humans; Intestinal Diseases, Parasitic; Intestinal Mucosa; Male; Mast Cells; Mastocytosis; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Rats; Rats, Wistar; Strongyloides; Strongyloidiasis