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The Journal of Immunology, 2003, 171: 6105-6111.
Copyright © 2003 by The American Association of Immunologists

Mac-1, but Not LFA-1, Uses Intercellular Adhesion Molecule-1 to Mediate Slow Leukocyte Rolling in TNF-{alpha}-Induced Inflammation 1

Jessica L. Dunne*, Robert G. Collins{ddagger}, Arthur L. Beaudet§, Christie M. Ballantyne and Klaus Ley2,*,{dagger}

* Department of Biomedical Engineering and {dagger} Cardiovascular Research Center, University of Virginia Health Sciences Center, Charlottesville, VA 22908; and Departments of {ddagger} Pediatrics, § Medicine, and Human Genetics, Baylor College of Medicine, Houston, TX 77030

We have previously shown that Mac-1 and LFA-1 play a cooperative role in slow leukocyte rolling in inflamed vessels, and that, although both have a role in leukocyte adhesion, the contribution from LFA-1 exceeds that of Mac-1. In this study, we used mice deficient in ICAM-1 (ICAM-1null) to study the function of ICAM-1 as an endothelial ligand for Mac-1 and LFA-1. The cremaster muscles of these mice were treated with TNF-{alpha} and prepared for intravital microscopy. We found that the average rolling velocity in venules was not different in ICAM-1null mice (4.7 µm/s) compared with wild-type mice (5.1 µm/s). Similarly, leukocyte adhesion efficiency in ICAM-1null mice (0.11 ± 0.01 mm) was similar to that in Mac-1-/- (0.12 ± 0.03 mm) mice but significantly increased compared with that in LFA-1-/- (0.08 ± 0.01 mm) mice and significantly reduced from that in wild type (0.26 ± 0.04 mm). When both LFA-1 and ICAM-1 were blocked, rolling velocity increased, and adhesion efficiency and arrest decreased. However, blocking both Mac-1 and ICAM-1 had no greater effect than either blockade alone. We conclude that endothelial ICAM-1 is the main ligand responsible for slow leukocyte rolling mediated by Mac-1, but not LFA-1.




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