Control of leukocyte rolling velocity in TNF- –induced inflammation by LFA-1 and Mac-1

Previously it was shown that 2-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the 2-integrins, L 2 (LFA-1) or M 2 (Mac1), were used to determine which of the 2-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factorand prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1 / mice (11.0 0.7 m/s) and Mac-1 / mice (10.1 1.1 m/s) compared to wild-type mice (4.8 0.3 m/s; P < .05), but were lower than in CD18 / mice (28.5 2.1 m/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. (Blood. 2002;99: 336-341)