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Published online 27 March 2006 doi:10.1084/jem.20052530
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 4, 907-917
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ARTICLE

 Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis

Jesús Rivera-Nieves1,4, Tracy L. Burcin2,3, Timothy S. Olson4, Margaret A. Morris2,3, Marcia McDuffie4,5, Fabio Cominelli1,4, and Klaus Ley2,3,6

1 Digestive Health Center of Excellence, 2 Robert M. Berne Cardiovascular Research Center, 3 Department of Biomedical Engineering, 4 Internal Medicine, 5 Microbiology and 6 Molecular Physiology and Biological Physics, University of Virginia Health Sciences Center, Charlottesville, VA 22908

CORRESPONDENCE Jesús Rivera-Nieves: jr3u{at}virginia.edu

L-selectin ligands might be relevant for inflammatory cell trafficking into the small intestine in a spontaneous model of chronic ileitis (i.e., SAMP1/YitFc mice). Immunoblockade of peripheral node addressin or mucosal addressin cell adhesion molecule 1 failed to ameliorate ileitis, whereas P-selectin glycoprotein ligand 1 (PSGL-1) neutralization attenuated both the adoptively transferred and spontaneous disease. PSGL-1 was detected in venules of mesenteric lymph node and small intestine by immunohistochemistry and confirmed by real-time reverse transcription polymerase chain reaction and flow cytometry. In addition, reconstitution of wild-type mice with PSGL-1–/– bone marrow demonstrated that PSGL-1 messenger RNA and PSGL-1 protein expression remained on endothelium, localized within mesenteric lymph node and small intestine. Endothelial PSGL-1 bound P-selectin–IgG and its blockade or genetic deletion altered the recruitment of lymphocytes to the small intestine, as revealed by intravital microscopy and homing studies. Endothelial expression of PSGL-1 adds a new dimension to the various cellular interactions involved in small intestinal recruitment. Thus, the multiple roles of PSGL-1 may explain why targeting this single adhesion molecule results in attenuation of chronic murine ileitis, a disease previously resistant to antiadhesion molecule strategies.

Abbreviations used: CD, Crohn's disease; FSC, forward light scatter; HEV, high endothelial venule; HRP, horseradish peroxidase; LP, lamina propria; MAdCAM-1, mucosal addressin cell adhesion molecule; MLN, mesenteric lymph node; PNAd, peripheral node addressin; PSGL-1, P-selectin glycoprotein ligand 1; SSC, side light scatter; UC, ulcerative colitis.


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