THE P-SELECTIN GLYCOPROTEIN LIGAND-1 IS IMPORTANT FOR RECRUITMENT OF NEUTROPHILS INTO INFLAMED MOUSE PERITONEUM

The P-selectin glycoprotein ligand-1 (PSGL-1) is a high-affinity ligan d of P-selectin on myeloid cells and certain subsets of lymphoid cells . We generated the rat monoclonal antibody (MoAb) 2PH1 that recognizes an epitope within the first 19 amino acids at the N terminus of the p rocessed form of mouse PSGL-1, This antibody blocks attachment of mous e myeloid cells to P-selectin under both static and flow conditions. I ntravenous administration of saturating amounts of 2PH1 reduced the nu mber of rolling leukocytes in venules of the acutely exposed mouse cre master muscle by 79% (+/-5.7%), whereas an anti-P-selectin MoAb reduce d it completely. Examining the effect of the MoAb 2PH1 on the recruitm ent of neutrophils into chemically inflamed mouse peritoneum showed th at blocking PSGL-1 inhibited neutrophil accumulation in the peritoneum by 82% (+/-7%) at 2 hours and by 59% (+/-79%) at 4 hours after stimul ation, A similar effect was seen with the MoAb against P-selectin. Sim ultaneous administration of both antibodies at the 4-hour time point b locked neutrophil accumulation by 85% (+/-4.2%), arguing for an additi onal partner molecule for PSGL-1 besides P-selectin, This is the first demonstration of the importance of PSGL-1 in the recruitment of mouse neutrophils into inflamed tissue. (C) 1997 by The American Society of Hematology.