title: Lactoferrin inhibits the binding of lipopolysaccharides to L-selectin and subsequent production of reactive oxygen species by neutrophils.
abstract: The activation of leukocytes by lipopolysaccharides (LPS), resulting in the oxidative burst, contributes to the pathogenesis of septic shock. The binding of LPS to L-selectin, which was reported as a serum-independent LPS receptor on neutrophils, induces the production of oxygen free radicals. Human lactoferrin (hLf), an anti-inflammatory glycoprotein released from neutrophil granules during infection, binds to LPS. In this study, we investigated the capacity of hLf to inhibit the L-selectin-mediated activation of neutrophils. Our experiments revealed that hLf prevents the binding of LPS to L-selectin in a concentration-dependent manner. Inhibition was maximum (87.7+/-0.5%) at a concentration of 50 microg/ml of hLf. Furthermore, hLf inhibited up to 55.4+/-0.5% of the intracellular hydrogen peroxide production induced by LPS in neutrophils. These findings suggest that the anti-inflammatory properties of hLf are due, at least in part, to their ability to prevent the binding of LPS to neutrophil L-selectin.
authors.affiliation: Laboratoire de Chimie Biologique, Unité Mixte de Recherche du CNRS no. 8576, Université des Sciences et Technologies de Lille, 59655, Villeneuve d'Ascq, France.
authors.forename: S
authors.initials: S
authors.lastname: Baveye
authors.forename: E
authors.initials: E
authors.lastname: Elass
authors.forename: J
authors.initials: J
authors.lastname: Mazurier
authors.forename: D
authors.initials: D
authors.lastname: Legrand
mesh_terms: D004926:Escherichia coli; D005434:Flow Cytometry; D005456:Fluorescent Dyes; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism*; D007781:Lactoferrin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D019041:L-Selectin; D006861:Hydrogen Peroxide; D007781:Lactoferrin