Mac-1, but not LFA-1, uses intercellular adhesion molecule-1 to mediate slow leukocyte rolling in TNF-alpha-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-alpha and prepared for intravital microscopy. We found that the average rolling velocity in venules was not different in ICAM-1(null) mice (4.7 micro m/s) compared with wild-type mice (5.1 micro m/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.
Dunne
Jessica L
JL
Department of Biomedical Engineering and Cardiovascular Research Center, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Collins
Robert G
RG
Beaudet
Arthur L
AL
Ballantyne
Christie M
CM
Ley
Klaus
K
D000818:Animals; D001783:Blood Flow Velocity; D002448:Cell Adhesion / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D036904:Leukocyte Rolling / Q000235:genetics / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D011237:Predictive Value of Tests; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*; D014699:Venules / Q000378:metabolism / Q000473:pathology
D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1