Neutrophils use both shared and distinct mechanisms to adhere to selectins under static and flow conditions.
Both P-selectin glycoprotein ligand-1 (PSGL-1) and L-selectin are localized on the microvilli of neutrophils and have been implicated in the attachment of neutrophils to P-selectin or E-selectin. We directly compared the attachment and rolling of neutrophils on P-selectin and E-selectin under flow, with emphasis on the functions of PSGL-1 and L-selectin. Flowing neutrophils attached more avidly and rolled at lower velocities on P-selectin than on E-selectin at matched densities. Studies with purified molecules indicated that P-selectin and E-selectin bound to a related site on PSGL-1 that overlapped the epitope for the anti-PSGL-1 mAb PL1. E-selectin bound with lower affinity than P-selectin to this site and also bound to an additional site(s) on PSGL-1.PL1 abolished adhesion of neutrophils to P-selectin under shear or static conditions, whereas DREG-56, a mAb to L-selectin, had no effect on adhesion to P-selectin. PL1 inhibited attachment of neutrophils to E-selectin under flow but not static conditions. DREG-56 also inhibited attachment of flowing neutrophils to E-selectin, and a combination of DREG-56 and PL1 nearly eliminated attachment to E-selectin under flow. These data suggest that PSGL-1 functions cooperatively with L-selectin to mediate optimal attachment of flowing neutrophils to E-selectin but not to P-selectin. Neutrophils attach more efficiently and with greater strength to P-selectin, perhaps because of the higher affinity of P-selectin for the PL1-defined site on PSGL-1.
Patel
K D
KD
Department of Medicine, W. K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
Moore
K L
KL
Nollert
M U
MU
McEver
R P
RP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016466:CHO Cells; D002448:Cell Adhesion; D006224:Cricetinae; D019040:E-Selectin / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D019041:L-Selectin / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology*; D013718:Tensile Strength
D000911:Antibodies, Monoclonal; D019040:E-Selectin; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D019041:L-Selectin