We had previously shown that the specific binding of endotoxin (lipopolysaccharide, LPS) to human monocytes in the presence of serum was mediated by the polysaccharide moiety of the LPS molecule. CD14 has been identified as the main receptor for endotoxin on monocytes/macrophages. In the present report we demonstrate that the CD14 molecule exhibits lectin-like properties. Anti-CD14 monoclonal antibodies inhibited the binding of [3H]-radiolabeled Neisseria meningitidis LPS as efficiently as the homologous unlabeled LPS. Rough Escherichia coli LPS (Rc- and Re-types) could also inhibit the binding of [3H]-LPS to a similar extent, whereas lipid A had no or very weak inhibitory activity. This suggests a major contribution of the inner-core region within the LPS and particularly the Kdo sugars. The lectin-like nature of CD14 was assessed with polyanionic sugars as well as with uncharged polysaccharides. The relative efficiencies in competition were dextran sulfate > fucoidan > mannan > polygalacturonic acid = heparan sulfate ≥ heparin ≥ chondroitin sulfate. Candida albicans phospholipomannan was far more active in the competition experiment than the mannan, indicating that, besides the osidic residues, anionic charges and/or fatty acids may contribute to the interaction with the CD14 molecule. Binding of polysaccharide to CD14 was not sufficient to trigger TNFα and IL-6 production since phospholipomannan and dextran sulfate were unable to induce cytokine release. Taken together, these results demonstrate that the binding of [3H]-LPS to CD14 involves the contribution of sugars and suggest that the signals for cytokine production require additional interactions.
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