P-, E- and l-selectin mediate leukocyte rolling in vivo at different characteristic velocities

Selectin-rnediated leukocyte rolling in vonules is a necessary step for inflammatory cell recruitment in vivo. Previous studies have established distinct reductions of leukocyte rolling flux in gene-targeted mire lacking P- selectin (P-) or L-selectin (L-), but not in E-selectin (E-) deficient mice. Here, we investigate leukocyte rolling velocities in cremaster venules of wild type (wt), P-, L- and E- mice. Studies were done in hemodynamically similar (wall shear rate 400-800 s^-1) venules of the exteriorized cremaster muscle using intravital microscopy. At <30 min after surgical trauma, we find rolling velocities between 20-40 μm/s in both wt and L- mice and no rolling in P- mice. At >50 min. rolling velocities increase to 50 μm/s in wt and 80 μm/s in L- mice, and P- mice show intermittent L-selectin dependent leukocyte rolling with average velocities around 130 p/s. After treatment with TNF, leukocyte rolling velocity is reduced to 5-6 μm/s in wt, L- or P- mice. By contrast, rolling in TNF-treated E- mice remains much higher (22 μ/s). These data show that, at the site densities prevailing in venules in vivo, E-selectin is responsible for slow leukocyte rolling after TNF, P-selectin mediates rolling at 20-40 //m/s, and L-selectin supports intermittent, rapid rolling. This work identifies a oreviouslv unrecoenized ohenotvoic defect of leukocyte rolling in E-selectin deficient mice.