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Biomedical subjects

A Muchmore

Publications and source records attributed to A Muchmore.

5 recordsLinked to original sources
PubMed1991

Evidence that specific high mannose structures directly regulate multiple cellular activities.

Previous studies have demonstrated that much of the immunomodulatory activity of the glycoprotein uromodulin can be attributed to attached oligosaccharides. Structural studies of isolated and purified saccharides derived from uromodulin suggest that the structure Man6GlcNAc2-asn can inhibit in vitro assays of antigen driven T cell proliferation. Based on these observations, we isolated a series of high mannose glycopeptides from a variety of natural sources and tested them for biological activity in a number of assays. We found that purified mannose rich glycopeptides are able to activate the hexose monophosphate (HMP) shunt, induce prostaglandin synthesis, and directly stimulate IL-1 synthesis. These in vitro effects appear to have in vivo counterparts. Thus in a species-restricted fashion, high mannose compounds are able to directly activate a delayed mononuclear cell infiltrate after intradermal injection. Our data suggest that specific mannose oligosaccharides may activate as well as inhibit cellular immune responses at several different levels. These findings support the hypothesis that specific saccharide structures could participate in the physiologic regulation of the immune response.

Animals↗
PubMed1990

Evidence that high mannose glycopeptides are able to functionally interact with recombinant tumor necrosis factor and recombinant interleukin 1.

Both recombinant tumor necrosis factor (rTNF) and recombinant interleukin 1 (rIL-1) are able to mediate vascular collapse and death in a previously described murine model, using galactosamine to enhance the toxicity of these cytokines. Unexpectedly, both acid-treated tumor necrosis factor (TNF) and a site-specifically mutagenized form of interleukin 1 (IL-1) (His-30----Arg-30), which fails to bind to the IL-1 receptor, retain full in vivo toxicity in this model of TNF- and IL-1-mediated shock. Previous studies have shown that rTNF and rIL-1 exhibit two functionally distinct binding regions. Both cytokines bind to their respective cell surface receptors and they also express lectin like binding specificity (Muchmore and Decker, J. Biol. Chem., 261: 13404-13407, 1986; Muchmore and Decker, J. Immunol., 138: 2541-2546, 1987) for defined oligosaccharides. The specificity of these two types of interactions is quite different. Cell surface receptors for IL-1 and TNF demonstrate essentially no cross-reactivity, whereas, in the case of carbohydrate binding, competition studies reveal an almost identical carbohydrate specificity for the structure Man5(6)GlcNAc2-Asn. Man5(6)GlcNAc2-Asn binding is either unaffected or actually enhanced by either acid treatment of rTNF or mutation at His-30 for rIL-1. Both deoxymannojirimycin and swainsonine, inhibitors of glycoprotein processing, raise intracellular levels of Man5-9GlcNAc2 and enhance the in vitro biological activity of both rTNF and rIL-1. Conversely, castanosperimine, a glucosidase I inhibitor which blocks the synthesis of mature high mannose structures, inhibits the biological activity of IL-1. These observations support the hypothesis that some effects of IL-1 and TNF may involve interaction with high mannose-substituted glycoproteins.

Animals↗
PubMed1980

Inhibition of DRw antisera reactivity by mono and oligosaccharides.

Mono and oligosaccharides were used to inhibit the cytotoxicity of antisera detecting HLA-DRw antigens on monocytes isolated from peripheral blood. Certain sugars preferentially inhibited antisera detecting some DRw antigens and not others. Sera detecting HLA-A and B antigens were not inhibited with the sugars used. Anti-DRw sera blocked the attachment of radiolabeled sugars to monocytes with the same patterns as the reciprocal blocking of cytotoxicity by the sugars. The results were not consistent with the intrepretation that carbohydrates are an antigenic "component" of DRw specificity, but rather that the surface structures, possibly those bearing the DRw antigens, are receptors for mono and oligo saccharides.

Cellobiose↗