Control of leukocyte rolling velocity in TNF-alpha-induced inflammation by LFA-1 and Mac-1.
Previously it was shown that beta(2)-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the beta(2)-integrins, alpha(L)beta(2) (LFA-1) or alpha(M)beta(2) (Mac-1), were used to determine which of the beta(2)-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factor-alpha and prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1(-/-) mice (11.0 +/- 0.7 microm/s) and Mac-1(-/-) mice (10.1 +/- 1.1 microm/s) compared to wild-type mice (4.8 +/- 0.3 microm/s; P <.05), but were lower than in CD18(-/-) mice (28.5 +/- 2.1 microm/s). When both LFA-1 and Mac-1 were absent or blocked, rolling velocity became dependent on shear rate and approached that of CD18(-/-) mice. In addition, leukocyte adhesion efficiency was decreased in LFA-1(-/-) mice to near CD18(-/-) levels, but decreased only slightly in Mac-1(-/-) mice. Thus, both LFA-1 and Mac-1 contribute to slowing down rolling leukocytes, although LFA-1 is more important than Mac-1 in efficiently inducing firm adhesion.
Dunne
Jessica L
JL
Department of Biomedical Engineering and Cardiovascular Research Center, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Ballantyne
Christie M
CM
Beaudet
Arthur L
AL
Ley
Klaus
K
D000009:Abdominal Muscles / Q000098:blood supply; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000473:pathology; D005434:Flow Cytometry; D018390:Gene Targeting; D018056:Hemorheology; D007962:Leukocytes / Q000502:physiology*; 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; D014409:Tumor Necrosis Factor-alpha; D014657:Vasculitis / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D014699:Venules
D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D014409:Tumor Necrosis Factor-alpha