The vitronectin receptor (alpha v beta 3) is implicated, in cooperation with P-selectin and platelet-activating factor, in the adhesion of monocytes to activated endothelial cells.
In this study we have investigated the presence on endothelial cells of potential glycoprotein receptors, other than P-selectin, which are involved in the adhesion of monocytes at the early stages of activation. We report that the majority of cells binding to thrombin-activated endothelial cells from a peripheral blood mononuclear cell (PBMC) preparation are monocytes. The adhesion of PBMC to thrombin-activated, but not resting, endothelial cells was inhibited (66%) by a monoclonal antibody (mAb) directed against alpha v beta 3. Elutriated monocytes or a monocytic cell line (U937) were also inhibited by this antibody, its F(ab)'2 fragments and three other anti-(alpha v beta 3) mAbs. alpha v beta 3 isolated from endothelial-cell lysates significantly inhibited the adhesion of monocytes and U937 cells to endothelial cells. A peptide motif (RGDF) known to interact with alpha v beta 3 inhibited U937 cell adhesion to activated endothelial cells by 53%. Finally, an anti-(P-selectin) mAb (LYP20) or a platelet-activating factor (PAF)-receptor antagonist (WEB 2086) inhibited monocyte adhesion to activated endothelial cells. This study shows for the first time that alpha v beta 3 is implicated, in addition to P-selectin and PAF, in the adhesion of monocytes to activated endothelial cells.
Murphy
J F
JF
INSERM U331/Institut Pasteur de Lyon, Faculté de Médecine Alexis Carrel, France.
Bordet
J C
JC
Wyler
B
B
Rissoan
M C
MC
Chomarat
P
P
Defrance
T
T
Miossec
P
P
McGregor
J L
JL
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000502:physiology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D019007:P-Selectin; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D016024:Receptors, Cytoadhesin / Q000276:immunology / Q000502:physiology*; D019030:Receptors, Vitronectin; D013917:Thrombin / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D001381:Azepines; D016023:Integrins; D009842:Oligopeptides; D019007:P-Selectin; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D014230:Triazoles; C052518:WEB 2086; C084961:arginyl-glycyl-aspartyl-phenylalanine; D013917:Thrombin