P-SELECTIN GLYCOPROTEIN LIGAND-1 (PSGL-1) IS A LIGAND FOR L-SELECTIN IN NEUTROPHIL AGGREGATION

In inflammation, activated neutrophils adhere to endothelial cells and aggregate with one another. While beta(2)-integrin and L-selectin are essential for aggregation, their ligands remain to be identified. We have previously shown that L-selectin mediates a carbohydrate-dependen t interaction in aggregation (Simon et al: J Immunol 149:2765, 1992; R ochon et al: J Immunol 152:1385. 1994). We have suggested that the L-s electin counter-structure is a mucinlike protein and proposed that agg regation occurs through a two-step process involving L-selectin, beta( 2)-integrin, and their distinct counter-structures (Bennett et al: J L euk Biol 58:510, 1995). A candidate ligand for L-selectin is P-selecti n glycoprotein ligand-l (PSGL-1). a mucinlike protein on neutrophils t hat binds P- and E-selectin. Using flow cytometry we show that the num ber and size of neutrophil aggregates is reduced with Fab fragments of PL1, an anti-PSGL-1 monoclonal antibody that blocks the interaction b etween P-selectin and PSGL-1 (Moore et al: J Cell Biol 128:661, 1995). In addition, monoclonal antibodies to L-selectin and PSGL-1 were used simultaneously to modulate the availability of these adhesion molecul es on individual cell populations. The inhibition of aggregation by th ese antibodies is consistent with L-selectin and PSGL-1 being counter- structures. We suggest that L-selectin and PSGL-1 support a collisiona l cell-cell interaction that represents the first step in neutrophil a ggregation. (C) 1996 by The American Society of Hematology.