A synthetic analog of the 3-deoxy-D-manno-2-octulosonic acid disaccharide moiety of rough-type endotoxins does not bind to mouse peritoneal macrophages and human monocytes.
Strong evidence supports the concept that lipid A is the main biologically active region of endotoxins and is recognized by specific binding sites of different cell types. However, receptors for carbohydrates are also present on mononuclear phagocytes, and it has been suggested that one of these lectin-like proteins may be specific for the 3-deoxy-D-manno-2-octolosonic acid (Kdo) residues of endotoxins. To reexamine this hypothesis, we prepared a 125I-labeled conjugate consisting of a synthetic Kdo-2,4-Kdo disaccharide covalently linked to bovine serum albumin (125I-Kdo2-BSA). The Kdo disaccharide residues of this radiolabeled conjugate were fully accessible to a monoclonal antibody which reacts specifically with this epitope. However, 125I-Kdo2-BSA did not exhibit any detectable specific binding on thioglycolate-elicited mouse peritoneal macrophages or on human monocytes. Furthermore, the specific binding of biotin-labeled lipopolysaccharide derivatives to mouse macrophages and human monocytes was not inhibited by a soluble synthetic Kdo-2,4-Kdo-polyacrylamide copolymer or by a synthetic glycolipid consisting of an alpha-Kdo residue glycosidically linked to O-6 of allyl-4-O-phosphoryl-N-3-hydroxytetradecanoyl-beta-D-glucosaminide. These results indicate that binding sites specific for Kdo are not present (or not accessible) on the surface of mouse macrophages and human monocytes.
Girard
R
R
Unité d'Immunophysiologie Moléculaire, URA-145 du Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France.
Pedron
T
T
Kosma
P
P
Chaby
R
R
D000818:Animals; D004187:Disaccharides / Q000378:metabolism*; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000032:analysis*; D013400:Sugar Acids / Q000378:metabolism*
D004187:Disaccharides; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D013400:Sugar Acids; C002532:2-keto-3-deoxyoctonate