In:
Journal of Leukocyte Biology, Oxford University Press (OUP), Vol. 81, No. 5 ( 2007-05-01), p. 1269-1275
Abstract:
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 ∼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.
Type of Medium:
Online Resource
ISSN:
0741-5400
,
1938-3673
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2007
detail.hit.zdb_id:
2026833-6
SSG:
12
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