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

Previously it was shown that β₂-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the β₂-integrins, α_Lβ₂ (LFA-1) or α_Mβ₂ (Mac-1), were used to determine which of the β₂-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factor-α and prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1^-/- mice (11.0 ± 0.7 μm/s) and Mac-1^-/- mice (10.1 ± 1.1 μm/s) compared to wild-type mice (4.8 ± 0.3 μm/s; P < .05), but were lower than in CD18^-/- mice (28.5 ± 2.1 μm/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.