Lactoferrin inhibits the binding of lipopolysaccharides to L-selectin and subsequent production of reactive oxygen species by neutrophils.
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.
Baveye
S
S
Laboratoire de Chimie Biologique, Unité Mixte de Recherche du CNRS no. 8576, Université des Sciences et Technologies de Lille, 59655, Villeneuve d'Ascq, France.
Elass
E
E
Mazurier
J
J
Legrand
D
D
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*
D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D019041:L-Selectin; D006861:Hydrogen Peroxide; D007781:Lactoferrin