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.