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 biologic ally active region of endotoxins and is recognized by specific binding sites of different cell types. However, receptors for carbohydrates a re also present on mononuclear phagocytes, and it has been suggested t hat 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 I-125-labeled conjugate consisting of a synthetic Kdo-2,4-Kdo disaccharide covalently linked to bovine serum albumin (I-125-Kdo2-BSA). The Kdo disaccharide residues of this radiol abeled conjugate were fully accessible to a monoclonal antibody which reacts specifically with this epitope. However, I-125-Kdo2-BSA did not exhibit any detectable specific binding on thioglycolate-elicited mou se peritoneal macrophages or on human monocytes. Furthermore, the spec ific binding of biotin-labeled lipopolysaccharide derivatives to mouse macrophages and human monocytes was not inhibited by a soluble synthe tic Kdo-2,4-Kdo-polyacrylamide copolymer or by a synthetic glycolipid consisting of an alpha-Kdo residue glycosidically linked to O-6 of ryl -N-3-hydroxytetradecanoyl-beta-D-glucosaminide. These results indicate that binding sites specific for Kdo are not present (or not accessibl e) on the surface of mouse macrophages and human monocytes.