HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Published online before print February 22, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: jlb.1206758v1 81/5/1269    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kukulski, F. Articles by Sévigny, J. Search for Related Content PubMed PubMed Citation Articles by Kukulski, F. Articles by Sévigny, J.

(Journal of Leukocyte Biology. 2007;81:1269-1275.)
© 2007 by Society for Leukocyte Biology

Extracellular nucleotides mediate LPS-induced neutrophil migration in vitro and in vivo

Filip Kukulski^*, Fethia Ben Yebdri^*, Julie Lefebvre^*, Michel Warny, Philippe A. Tessier and Jean Sévigny^*,1

Centres de Recherche en
^* Rhumatologie et Immunologie and
Infectiologie, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, Canada; and
Acambis, Inc., Cambridge, Massachusetts, USA

¹ Correspondence: Centre de Recherche en Rhumatologie et Immunologie, Université Laval, 2705, Boulevard Laurier, local T1-49, Québec, QC, G1V 4G2, Canada. E-mail: jean.sevigny{at}crchul.ulaval.ca

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.

Key Words: inflammation • monocyte • IL-8 • P2 receptor

This article has been cited by other articles:

				I. Bar, P.-J. Guns, J. Metallo, D. Cammarata, F. Wilkin, J.-M. Boeynams, H. Bult, and B. Robaye Knockout Mice Reveal a Role for P2Y6 Receptor in Macrophages, Endothelial Cells, and Vascular Smooth Muscle Cells Mol. Pharmacol., September 1, 2008; 74(3): 777 - 784. [Abstract] [Full Text] [PDF]

				R. W. S. Li, R. Y. K. Man, P. M. Vanhoutte, and G. P. H. Leung Stimulation of ecto-5'-nucleotidase in human umbilical vein endothelial cells by lipopolysaccharide Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1177 - H1181. [Abstract] [Full Text] [PDF]

				D. M. Grbic, E. Degagne, C. Langlois, A.-A. Dupuis, and F.-P. Gendron Intestinal Inflammation Increases the Expression of the P2Y6 Receptor on Epithelial Cells and the Release of CXC Chemokine Ligand 8 by UDP J. Immunol., February 15, 2008; 180(4): 2659 - 2668. [Abstract] [Full Text] [PDF]