LEUKOCYTE ROLLING IN-VIVO IS MEDIATED BY P-SELECTIN GLYCOPROTEIN LIGAND-1

Leukocyte rolling, an early and important step in the inflammatory res ponse, is mediated by the selectin family of adhesion molecules. The s electins bind with low affinity to sialylated and fucosylated glycans such as sialyl Lewis(x) (sLe(x)), but bind with high affinity to only a few specific glycoproteins on cell surfaces. One such glycoprotein i s P-selectin glycoprotein ligand-1 (PSGL-1). The relative contribution s of low- and high-affinity ligands to leukocyte rolling in vivo are u nknown. We show here that a monoclonal antibody to PSGL-1 (PL1) dramat ically reduces rolling of human polymorphonuclear neutrophils (PMN) an d promyelocytic HL-60 cells in venules of acutely exteriorized rat mes entery. Control PMN and HL-60 cell rolling flux fractions were 39% +/- 3% and 33% +/- 5%, which were reduced by PL1 to 7% +/- 2% and 6% +/- 2%, respectively. Similar reductions were seen with F(ab) fragments of PL1. PL1-treated PMN rolled at significantly higher mean velocities t han untreated PMN owing to intermittent rather that continuous interac tions. These findings show that interaction of P-selectin with PSGL-1 is required for rolling of myeloid cells in mesenteric venules at phys iologic shear stress in vivo. (C) 1996 by The American Society of Hema tology.