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.