Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo
Open Access
- 22 February 2007
- journal article
- extracellular mediators-and-effector-molecules
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 81 (5), 1269-1275
- https://doi.org/10.1189/jlb.1206758
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.Keywords
Funding Information
- Canadian Institutes of Health Research
- CIHR (MOP-68957)
- Arthritis Society
- TAS (01/0078)
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