Role for L-selectin in lipopolysaccharide-induced activation of neutrophils.
The activation of leucocytes by bacterial cell wall lipopolysaccharide (LPS) contributes to the pathogenesis of septic shock. LPS is known to interact with several cell-surface proteins, including CD14, when presented as a complex with serum LPS-binding protein. However, the identity of the receptor responsible for LPS signalling and leucocyte activation is unknown. Interestingly, mice deficient in cell-surface L-selectin were dramatically resistant to the lethal effects of high doses of LPS in a model of septic shock. Recently we reported that L-selectin binds to cardiolipin and other charged phospholipids at a site distinct from the carbohydrate-binding site. Structural similarities between charged phospholipids and the lipid A moiety of LPS prompted us to investigate interactions between L-selectin and LPS. Herein we show that L-selectin is a neutrophil surface receptor for LPS and lipotechoic acid. The binding of LPS to L-selectin is independent of serum and Ca2+, and is blocked by antibodies to L-selectin and fucoidan. Furthermore, the interaction of LPS with cell-surface L-selectin results in superoxide production, indicating that L-selectin can mediate both binding and activation of human neutrophils. These findings suggest novel therapeutic approaches for the treatment of septic shock.
Malhotra
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Glycobiology Research Unit, Glaxo Wellcome Medicines Research Centre, Stevenage, Herts, 2NY, U.K.
Priest
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Bird
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MI
D000818:Animals; D006801:Humans; D007700:Kinetics; D019041:L-Selectin / Q000097:blood* / Q000502:physiology; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity; D013481:Superoxides / Q000097:blood; D013682:Teichoic Acids / Q000378:metabolism
D008070:Lipopolysaccharides; D013682:Teichoic Acids; D013481:Superoxides; D019041:L-Selectin; C009900:lipoteichoic acid