Stimulation of P-selectin glycoprotein ligand-1 on mouse neutrophils activates beta 2-integrin mediated cell attachment to ICAM-1.
The entry of neutrophils into inflamed tissues is initiated by cell rolling on the blood vessel wall followed by arrest and transendothelial migration. Rolling is mediated by the selectins, while the two subsequent steps require activated beta 2-integrins. We have investigated whether the binding of P-selectin to mouse neutrophils could trigger the activation of beta 2-integrins. We show that cross-linking of P-selectin glycoprotein ligand-1 (PSGL-1) on mouse neutrophils with an antibody-like recombinant form of P-selectin or with monoclonal antibodies stimulated the production of reactive oxygen intermediates and enhanced neutrophil attachment to intercellular adhesion molecule 1 (ICAM-1)-expressing CHO cells. This effect was independent of whether complete antibodies or F(ab')2 fragments were used. The adhesion-stimulating effect of P-selectin could be blocked by monoclonal antibodies against PSGL-1. Increase of cell attachment was dependent on lymphocyte function-associated antigen 1 (LFA-1) and on Mac-1, since it could be blocked with antibodies against both respective integrin alpha-chains. Moreover, cell surface expression of Mac-1 increased upon cross-linking of PSGL-1. In agreement with published data, treatment of human neutrophils with P-selectin-IgG did not enhance attachment to ICAM-1. Our data suggest that ligation of PSGL-1 on mouse neutrophils, but not on human neutrophils, activates beta 2-integrin mediated cell attachment to ICAM-1.
Blanks
J E
JE
Institute of Cell Biology, ZMBE, University of Münster, Germany.
Moll
T
T
Eytner
R
R
Vestweber
D
D
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism / Q000502:physiology*; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D006224:Cricetinae; D003432:Cross-Linking Reagents; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism*; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
D018821:CD18 Antigens; D003432:Cross-Linking Reagents; D007074:Immunoglobulin G; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1