Triggering of beta 1-integrin chain induces platelet adhesion to cultured endothelium.
We report here that platelets adhere to cultured endothelial cells (EC) on exposure to the integrin beta 1 activating monoclonal antibody (mAb) BV7. The effect of BV7 is exerted mostly on platelets rather than EC. BV7 does not induce platelet aggregation or 5-hydroxytyptamine (5-HT) release and does not increase platelet adhesion to matrix proteins. Another activating beta 1 mAb, Lia1/2, triggers an effect similar to BV7. Blocking antibodies to alpha 2 and beta 1, but not to other integrin chains, are able to inhibit BV7-mediated adhesion. Moreover, the effect of BV7 requires active cellular metabolism and is not inhibited by platelet treatment with aspirin, by the PAF receptor antagonist BN50730, the phosphokinase C inhibitor staurosporin, or by the cAMP or cGMP enhancers prostaglandin E1 and sodium nitroprusside, respectively. Finally, BV7-mediated adhesion was enhanced by the endoperoxide analogue U46619. These data describe a novel mechanism of platelet adhesion to endothelial cells. This adhesion pathway appears to be mediated by alpha 2 beta 1-integrin on platelets and a still-undefined endothelial counter receptor.
Del Maschio
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A
Laboratory of Vascular Biology and Human Immunology, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. delmaschio@irfmn.mnegri.it
Martín-Padura
I
I
Bernasconi
S
S
Dejana
E
E
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009599:Nitroprusside / Q000494:pharmacology; D019007:P-Selectin / Q000096:biosynthesis; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012701:Serotonin / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001381:Azepines; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D058924:Thienopyridines; D014230:Triazoles; C039351:platelet activating factor receptor; C066686:BN 50730; D009599:Nitroprusside; D012701:Serotonin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000527:Alprostadil; D006152:Cyclic GMP; D019311:Staurosporine; D001241:Aspirin