Neutrophil adherence to human endothelium in vitro occurs by CDw18 (Mo1, MAC-1/LFA-1/GP 150,95) glycoprotein-dependent and -independent mechanisms.
Components of the CDw18 leukocyte surface glycoprotein complex (Mo1/LFA-1/GP 150,95 or MAC-1, LFA-1 family) are required for some adhesion-related functions of human neutrophils (PMNs). We evaluated the ability of monoclonal antibodies (MoAb) directed against specific determinants on the CDw18 glycoproteins to inhibit neutrophil adherence to cultured human endothelial cells (EC) stimulated by a variety of agonists, including thrombin and leukotriene C4, which induce the EC-dependent adhesion of PMNs. MoAb 60.3, an antibody that binds to an epitope common to the 3 heterodimer subunits of the neutrophil CDw18 complex, potently inhibited (90-100%) the rapid (5-30 minute) adherence response stimulated by N-formyl-methyionyl-leucyl-phenylalanine, leukotriene B4, platelet-activating factor, phorbol myristate acetate, Ionophore A23187, and tumor necrosis factor. MoAbs directed against epitopes on the alpha polypeptide of the CD11b (Mol, MAC-1) heterodimer also inhibited PMN adherence to EC and to cell-free surfaces induced by these agonists. In contrast, the anti-CDw18 MoAbs had a trivial effect on maximal EC-dependent neutrophil adherence stimulated by thrombin and leukotriene C4, and incompletely inhibited PMN adherence induced by these agonists under submaximal conditions. These findings indicate that there is an alternative mechanism for neutrophil adherence, presumably resulting from molecular alterations of the EC surface, that does not require the PMN CDw18 glycoproteins. They also suggest that the inability to adhere to endothelium may not completely account for the defect in chemotaxis that is observed in vivo in neutrophils that are deficient in the CDw18 complex.
Zimmerman
G A
GA
Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah School of Medicine, Salt Lake City 84112.
McIntyre
T M
TM
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000166:cytology*; D013189:SRS-A / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D013189:SRS-A; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013917:Thrombin