P-selectin glycoprotein ligand-1 regulates chemokine-dependent leukocyte recruitment in colonic ischemia-reperfusion.
OBJECTIVE
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.


METHODS
Balb/c mice were used in an inverted intravital fluorescence microscopy study of the microvascular bed in the colon.


METHODS
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.
Santen
S
S
Department of Surgery, Malmö University Hospital, Lund University, 205 02 Malmö, Sweden.
Schramm
R
R
Menger
M D
MD
Wang
Y
Y
Jeppsson
B
B
Thorlacius
H
H
D000818:Animals; D002448:Cell Adhesion; D054426:Chemokine CXCL2 / Q000494:pharmacology; D003106:Colon / Q000098:blood supply*; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D036904:Leukocyte Rolling; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000276:immunology / Q000473:pathology; D008856:Microscopy, Fluorescence; D019007:P-Selectin / Q000378:metabolism*; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology
D054426:Chemokine CXCL2; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein