Potential non-glycoprotein IIb/IIIa effects of abciximab.
The antithrombotic effect of abciximab is believed to be primarily due to its blockade of platelet glycoprotein IIb/IIIa receptors, leading to the inhibition of platelet aggregation. Studies have, however, identified that antibody 7E3, the parent molecule of abciximab, and/or abciximab itself, binds to both "activated" alphaMbeta2 receptors and alphaVbeta3 receptors. Because alphaMbeta2 receptors are present on granulocytes and monocytes, cells that have been implicated in contributing to atherosclerosis, intimal hyperplasia after vascular injury, reperfusion injury, and thrombin generation, it is possible that some of abciximab's effects relate to this reactivity. Similarly, because alphaVbeta3 has been implicated in platelet adhesion to osteopontin, intimal hyperplasia after vascular injury, and platelet-mediated thrombin generation, it is possible that some of abciximab's beneficial effects relate to this reactivity. Blockade of alphaVbeta3 receptors may also be beneficial in other disease states because, in animal models, such blockade inhibits tumor angiogenesis and sickle cell adhesion to blood vessel endothelium. Despite these intriguing observations, there are no direct data to support any beneficial roles or any unwanted side effects related to the reactivities of abciximab with "activated" alphaMbeta2 or alphaVbeta3 receptors.
Coller
B S
BS
Samuel Bronfman Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
D000077284:Abciximab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology*; D006965:Hyperplasia / Q000517:prevention & control; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism / Q000494:pharmacology*; D016177:Macrophage-1 Antigen / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D019030:Receptors, Vitronectin / Q000187:drug effects* / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D016177:Macrophage-1 Antigen; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D000077284:Abciximab