CD14 LPS RECEPTOR EXHIBITS LECTIN-LIKE PROPERTIES/

Citation
Jm. Cavaillon et al., CD14 LPS RECEPTOR EXHIBITS LECTIN-LIKE PROPERTIES/, Journal of endotoxin research, 3(6), 1996, pp. 471-480
Citations number
56
Categorie Soggetti
Biology,Microbiology,"Medicine, Research & Experimental",Immunology
ISSN journal
09680519
Volume
3
Issue
6
Year of publication
1996
Pages
471 - 480
Database
ISI
SICI code
0968-0519(1996)3:6<471:CLRELP>2.0.ZU;2-2
Abstract
We had previously shown that the specific binding of endotoxin (lipopo lysaccharide, LPS) to human monocytes in the presence of serum was med iated 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 [H-3]-radiolabeled Neisseria meningitidis LPS as efficient ly as the homologous unlabeled LPS. Rough Escherichia coli LPS (Rc- an d Re-types) could also inhibit the binding of [H-3]-LPS to a similar e xtent, whereas lipid A had no or very weak inhibitory activity. This s uggests a major contribution of the inner-core region within the LPS a nd particularly the Kdo sugars. The lectin-like nature of CD14 was ass essed with polyanionic sugars as well as with uncharged polysaccharide s. The relative efficiencies in competition were dextran sulfate > fuc oidan > mannan > polygalacturonic acid = heparan sulfate greater than or equal to heparin greater than or equal to chondroitin sulfate. Cand ida albicans phospholipomannan was far more active in the competition experiment than the mannan, indicating that, besides the osidic residu es, anionic charges and/or fatty acids may contribute to the interacti on with the CD14 molecule. Binding of polysaccharide to CD14 was not s ufficient to trigger TNF alpha and IL-6 production since phospholipoma nnan and dextran sulfate were unable to induce cytokine release. Taken together, these results demonstrate that the binding of [H-3]-LPS to CD14 involves the contribution of sugars and suggest that the signals for cytokine production require additional interactions.