P-SELECTIN AND L-SELECTIN MEDIATE DISTINCT BUT OVERLAPPING FUNCTIONS IN ENDOTOXIN-INDUCED LEUKOCYTE-ENDOTHELIAL INTERACTIONS IN THE RAT MESENTERIC MICROCIRCULATION

Endotoxin is a potent stimulus of leukocyte infiltration, but the adhe sion-related mechanisms responsible for LPS-induced cell recruitment e vents in vivo remain poorly characterized. Utilizing intravital micros copy, we examined the role of P- and L-selectin in LPS-induced inflamm ation. We demonstrated that superfusion of rat mesentery with LPS resu lted in significant increases in both leukocyte rolling and adherence, which were maintained for at least 2 h. Pretreatment with a P-selecti n neutralizing mAb only partially inhibited LPS-induced leukocyte roll ing, but completely inhibited LPS-induced leukocyte adherence througho ut the 2-h observation period. Pretreatment with an L-selectin neutral izing mAb dramatically inhibited LPS-induced increases in leukocyte ro lling, but unlike the P-selectin mAb did not inhibit leukocyte adhesio n. Fucoidin, which blocks both P- and L-selectin function, completely inhibited LPS-induced leukocyte rolling and adhesion. Consistent with previous studies, leukocyte rolling velocities on P-selectin were obse rved to be far less than velocities observed for leukocytes rolling on L-selectin in vivo. These data suggest that P-selectin plays a role i n LPS-induced rolling and is essential for LPS-induced leukocyte adher ence, while L-selectin functions in LPS-induced rolling, but not in ad hesion.