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

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-1^null) 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-α and prepared for intravital microscopy. We found that the average rolling velocity in venules was not different in ICAM-1^null mice (4.7 μm/s) compared with wild-type mice (5.1 μm/s). Similarly, leukocyte adhesion efficiency in ICAM-1^null 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.