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Am J Physiol Gastrointest Liver Physiol 293: G1054-G1060, 2007. First published September 20, 2007; doi:10.1152/ajpgi.00350.2007
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INFLAMMATION/IMMUNITY/MEDIATORS

Mechanisms of platelet and leukocyte recruitment in experimental colitis

Thorsten Vowinkel,1,2 Katherine C. Wood,1 Karen Y. Stokes,1 Janice Russell,1 Anitaben Tailor,1 Christoph Anthoni,1,2 Norbert Senninger,2 Christian F. Krieglstein,2 and D. Neil Granger1

1Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and 2Department of General Surgery, University Hospital Münster, Münster, Germany

Submitted 31 July 2007 ; accepted in final form 19 September 2007

Both leukocytes and platelets accumulate in the colonic microvasculature during experimental colitis, leading to microvascular dysfunction and tissue injury. The objective of this study was to determine whether the recruitment of leukocytes and platelets in inflamed colonic venules are codependent processes. The rolling and adherence of leukocytes and platelets in colonic venules of mice with dextran sodium sulfate (DSS)-induced colitis were monitored by intravital videomicroscopy. DSS elicited an increased recruitment of both rolling and adherent leukocytes and platelets. DSS-colitic mice rendered thrombocytopenic with anti-platelet serum exhibited profound reductions in leukocyte adhesion. Neutropenia, induced with anti-neutrophil serum, significantly reduced the adhesion of leukocytes and the accumulation of platelet-leukocyte aggregates while greatly enhancing the number of platelets that roll and adhere directly to venular endothelial cells. The enhanced platelet adhesion associated with neutropenia was mediated by platelet P-selectin interactions with endothelial cell P-selectin glycoprotein ligand (PSGL-1). DSS colitis was also associated with an increased expression of PSGL-1 in the colonic vasculature. These findings indicate that the recruitment of leukocytes and platelets in inflamed colonic venules are codependent processes.

platelets; leukocytes; intravital microscopy; P-selectin; P-selectin glycoprotein ligand-1


Address for reprint requests and other correspondence: D. N. Granger, Dept. of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, Louisiana 71130-3932 (e-mail: dgrang{at}lsuhsc.edu)






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