The effects of GPIIb-IIIa antagonists and a combination of three other antiplatelet agents on platelet-leukocyte interactions.
The effects of the GPIIb-IIIa antagonists abciximab and MK-852 on platelet-leukocyte interactions in vitro were studied and the results compared with those obtained with a combination of aspirin, dipyridamole and AR-C69931 (Asp/Dip/AR-C). Platelet-monocyte (P/M) and platelet-neutrophil (P/N) conjugate formation increased when blood was stirred or a platelet agonist was added. Leukocyte activation also occurred as judged by expression of surface tissue factor antigen and CD11b. Abciximab and MK-852 potentiated P/M, especially when collagen was used. They also increased the amount of tissue factor on the monocytes, but not CD11b. The Asp/Dip/AR-C did not enhance P/M or tissue factor exposure. Augmented tissue factor expression on monocytes in the presence of a GPIIb-IIIa antagonist may be relevant to the increased mortality associated with trials of such antagonists when given orally in patients with vascular disease. The Asp/Dip/AR-C was superior to abciximab and MK-852 in inhibiting platelet and leukocyte function.
Zhao
Lian
L
Centre for Vascular Research, University of Nottingham, UK.
Bath
Philip M W
PM
Fox
Sue
S
May
Jane
J
Judge
Heather
H
Lösche
Wolfgang
W
Heptinstall
Stan
S
D000077284:Abciximab; D000249:Adenosine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects*; D039481:CD11b Antigen / Q000032:analysis; D004176:Dipyridamole / Q000008:administration & dosage; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D066298:In Vitro Techniques; D007962:Leukocytes / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D053778:Thiazolidines; D013925:Thromboplastin / Q000032:analysis
D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D007140:Immunoglobulin Fab Fragments; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D053778:Thiazolidines; C083231:MK 0852; D000249:Adenosine Monophosphate; D004176:Dipyridamole; C117446:cangrelor; D013925:Thromboplastin; D001241:Aspirin; D000077284:Abciximab