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-dependent interaction in aggregation (Simon et al: J Immunol 149:2765, 1992; Rochon et al: J Immunol 152:1385, 1994). We have suggested that the L-selectin counter-structure is a mucinlike protein and proposed that aggregation occurs through a two-step process involving L-selectin, beta 2-integrin, and their distinct counter-structures (Bennett et al: J Leuk Biol 58:510, 1995). A candidate ligand for L-selectin is P-selectin glycoprotein ligand-1 (PSGL-1), a mucinlike protein on neutrophils that binds P-and E-selectin. Using flow cytometry we show that the number and size of neutrophil aggregates is reduced with Fab fragments of PL1, an anti-PSGL-1 monoclonal antibody that blocks the interaction between 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 molecules on individual cell populations. The inhibition of aggregation by these antibodies is consistent with L-selectin and PSGL-1 being counter-structures. We suggest that L-selectin and PSGL-1 support a collisional cell-cell interaction that represents the first step in neutrophil aggregation.
Guyer
D A
DA
Cytometry, Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, USA.
Moore
K L
KL
Lynam
E B
EB
Schammel
C M
CM
Rogelj
S
S
McEver
R P
RP
Sklar
L A
LA
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D018821:CD18 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002449:Cell Aggregation / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D019041:L-Selectin / Q000502:physiology*; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D008666:Metalloendopeptidases / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018821:CD18 Antigens; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D019041:L-Selectin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008666:Metalloendopeptidases; C070738:O-sialoglycoprotein endopeptidase