Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo.
Extracellular nucleotides are emerging as important inflammatory mediators. Here, we demonstrate that these molecules mediate LPS-induced neutrophil migration in vitro and in vivo. Apyrase, a nucleotide scavenger, reduced the ability of LPS-stimulated monocytes to recruit neutrophils, as assayed using a modified Boyden chamber. This effect resulted from the inhibition of IL-8 release from monocytes. Furthermore, LPS-induced IL-8 release by monocytes was attenuated significantly by P2Y6 receptor antagonists, RB-2 and MRS2578. Reciprocally, UDP, the selective P2Y6 agonist, induced IL-8 release by monocytes. As for LPS, the media of UDP-stimulated monocytes were chemotactic for neutrophils; IL-8 accounted for approximately 50% of neutrophil migration induced by the media of LPS- or UDP-treated monocytes in transendothelial migration assays. It is important that in the murine air-pouch model, extracellular nucleotides were instrumental in LPS-induced neutrophil migration. Altogether, these data imply that LPS induces the release of nucleotides from monocytes and that by autocrine stimulation, the latter molecules regulate neutrophil migration caused by Gram-negative bacteria, suggesting a proinflammatory role of extracellular nucleotides in innate immunity.
Kukulski
Filip
F
Centre de Recherce en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Université Laval, 2705, Boulevard Laurier, local T1-49, Québec, QC, G1V 4G2, Canada.
Ben Yebdri
Fethia
F
Lefebvre
Julie
J
Warny
Michel
M
Tessier
Philippe A
PA
Sévigny
Jean
J
D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology; D045604:Extracellular Fluid / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D009711:Nucleotides / Q000378:metabolism*; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000276:immunology; D013329:Structure-Activity Relationship
D016209:Interleukin-8; D008070:Lipopolysaccharides; D009711:Nucleotides; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D001081:Apyrase