P-selectin glycoprotein ligand-1 regulates chemokine-dependent leukocyte recruitment in colonic ischemia-reperfusion |
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Authors: | S Santen R Schramm M D Menger Y Wang B Jeppsson H Thorlacius |
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Institution: | 1.Department of Surgery, Malm? University Hospital,Lund University,Malm?,Sweden;2.Department of Thoracic and Cardiovascular Surgery,University of Saarland,Homburg,Germany;3.Institute for Clinical and Experimental Surgery,University of Saarland,Homburg,Germany |
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Abstract: | Objective and design: Leukocyte recruitment is a key feature in ischemia-reperfusion (I/R) -provoked tissue injury. This study evaluated the role
of P-selectin-glycoprotein ligand-1 (PSGL-1) in CXC chemokine- and ischemia-reperfusion- induced leukocyte rolling and adhesion
in the colon.
Materials Balb/c mice were used in an inverted intravital fluorescence microscopy study of the microvascular bed in the colon.
Treatment: Mice were challenged with macrophage inflammatory protein-2 (MIP-2) intraperitonally and leukocyte-endothelium interactions
were analysed 3 h later. In separate experiments, mice were exposed to I/R by clamping of the superior mesenteric artery for
30 min and leukocyte rolling and adhesion were analysed after 120 min of reperfusion.
Results: MIP-2 dose-dependently increased leukocyte rolling and adhesion in the colon. Pretreatment with an anti-PSGL-1 antibody reduced
MIP-2-provoked leukocyte rolling and adhesion by more than 89%. I/R increased expression of MIP-2 as well as leukocyte rolling
and adhesion. Immunoneutralization of PSGL-1 decreased reperfusion-induced leukocyte rolling by 85% and adhesion by 93% in
colonic venules.
Conclusions: Our data demonstrates that PSGL-1 is a dominant adhesion molecule supporting MIP-2- and I/R-provoked leukocyte rolling. Inhibition
of PSGL-1 abolished leukocyte rolling and abrogated I/R-induced leukocyte adhesion in colonic venules. These findings suggest
that targeting PSGL-1 may be an effective strategy to prevent I/R-induced inflammation in the colon.
Received 4 December 2006; returned for revision 9 January 2007; accepted by M. Parnham 6 June 2007 |
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Keywords: | Adhesion Colon Inflammation Ischemia Microcirculation |
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