P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+ hematopoietic progenitor cells.
Selectins play a critical role in initiating leukocyte binding to vascular endothelium. In addition, in vitro experiments have shown that neutrophils use L-selectin to roll on adherent neutrophils, suggesting that they express a nonvascular L-selectin ligand. Using a L-selectin/IgM heavy chain (mu) chimeric protein as an immunocytological probe, we show here that L-selectin can bind to neutrophils, monocytes, CD34+ hematopoietic progenitors, and HL-60 and KG-1 myeloid cells. The interaction between L-selectin and leukocytes was protease sensitive and calcium dependent, and abolished by cell treatment with neuraminidase, chlorate, or O-sialoglycoprotein endopeptidase. These results revealed common features between leukocyte L-selectin ligand and the mucin-like P-selectin glycoprotein ligand 1 (PSGL-1), which mediates neutrophil rolling on P- and E-selectin. The possibility that PSGL-1 could be a ligand for L-selectin was further supported by the ability of P-selectin/mu chimera to inhibit L-selectin/mu binding to leukocytes and by the complete inhibition of both selectin interactions with myeloid cells treated with mocarhagin, a cobra venom metalloproteinase that cleaves the amino terminus of PSGL-1 at Tyr-51. Finally, the abrogation of L- and P-selectin binding to myeloid cells treated with a polyclonal antibody, raised against a peptide corresponding to the amino acid residues 42-56 of PSGL-1, indicated that L- and P-selectin interact with a domain located at the amino-terminal end of PSGL-1. The ability of the anti-PSGL-1 mAb PL-1 to inhibit L- and P-selectin binding to KG-1 cells further supported that possibility. Thus, apart from being involved in neutrophil rolling on P- and E-selectin, PSGL-1 also plays a critical role in mediating neutrophil attachment to adherent neutrophils. Interaction between L-selectin and PSGL-1 may be of major importance for increasing leukocyte recruitment at inflammatory sites.
Division of Hematology, University of Lausanne, Switzerland.
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Spertini
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Cordey
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Monai
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Giuffrè
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Schapira
D018952:Antigens, CD34; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002704:Chlorates / Q000494:pharmacology; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000502:physiology; D005434:Flow Cytometry; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D019041:L-Selectin / Q000096:biosynthesis / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D008666:Metalloendopeptidases / Q000494:pharmacology; D009000:Monocytes / Q000502:physiology*; D009439:Neuraminidase / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D018952:Antigens, CD34; D002704:Chlorates; D017931:DNA Primers; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D011993:Recombinant Fusion Proteins; D019041:L-Selectin; D009439:Neuraminidase; D008666:Metalloendopeptidases; C070738:O-sialoglycoprotein endopeptidase