LEUKOCYTE ROLLING IN VENULES OF STRIATED-MUSCLE AND SKIN IS MEDIATED BY P-SELECTIN, NOT BY L-SELECTIN

Leukocyte rolling in postcapillary venules is mediated by adhesion mol ecules of the selectin family expressed on both leukocytes (L-selectin ) and endothelial cells (E- and P-selectin). With the use of intravita l fluorescence microscopy, the effects of antibodies against these sel ectins were analyzed in the skinfold chamber model of BALB/c mice and the ear model of homozygous hairless mice (hr/kr) that permit chronic observation of striated muscle and skin microcirculation in awake anim als, respectively. Mice were injected intravenously with monoclonal an tibodies (MAb) to murine L-selectin and E-selectin and affinity-purifi ed polyclonal antibodies to P-selectin. The antibodies, which are know n to block cell adhesion, were tested by immunoprecipitation to select ively bind to L-, E-, or P-selectin. Leukocyte rolling was a constant finding in both microcirculation models in the absence of inflammatory stimuli. In both models, injection of anti-P-selectin antibodies comp letely prevented baseline leukocyte rolling over an observation period of 2 h (P < 0.01 vs. baseline), while no effects were seen after admi nistration of either anti-l-selectin or anti-E-selectin MAb. Treatment with the isotype-matched control antibodies did not affect leukocyte rolling in either model. We conclude that leukocyte rolling in postcap illary venules of murine striated muscle and skin is a physiological p rocess mediated via P-selectin, whereas L- and E-selectin appear not t o play a significant role under these circumstances.