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Extracellular nucleotides mediate LPS‐induced neutrophil migration in vitro and in vivo
Author(s) -
Kukulski Filip,
Ben Yebdri Fethia,
Lefebvre Julie,
Warny Michel,
Tessier Philippe A.,
Sévigny Jean
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1206758
Subject(s) - neutrophil extracellular traps , apyrase , extracellular , biology , chemotaxis , innate immune system , microbiology and biotechnology , n formylmethionine leucyl phenylalanine , proinflammatory cytokine , lipopolysaccharide , in vivo , inflammation , immunology , receptor , biochemistry
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 P2Y 6 receptor antagonists, RB‐2 and MRS2578. Reciprocally, UDP, the selective P2Y 6 agonist, induced IL‐8 release by monocytes. As for LPS, the media of UDP‐stimulated monocytes were chemotactic for neutrophils; IL‐8 accounted for ∼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.