on July 17, 2003
Published online before print July 17, 2003, doi: 10.1161/01.ATV.0000087035.46547.89
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Submitted on April 10, 2003
Accepted on June 10, 2003
Effect of Glycoprotein IIb/IIIa Antagonist Abciximab on Monocyte-Platelet Aggregates and Tissue Factor Expression
Sabine Steiner ;
From the Divisions of Angiology (S.S., D.S., E.M., C.W.K.) and Cardiology (K.H., C.K.), 2nd Department of Medicine, University of Vienna, Austria.
* To whom correspondence should be addressed. E-mail: christoph.kopp{at}univie.ac.at.
Objective--Activated platelets rapidly adhere to monocytes and upregulate the expression of tissue factor (TF), the major trigger of the coagulation cascade. In this study, we examined the effect of abciximab, a nonselective glycoprotein IIb/IIIa-receptor antagonist, on monocyte TF expression in thrombin receptor activator-stimulated whole blood in vitro.
Methods and Results--Abciximab (50 µg/mL) reduced the mass of platelets attached to monocytes, measured by the mean fluorescence intensity (MFI) of CD42b on CD14+ cells, 1 (CD42b, 471±197 versus 1073±217 MFI, mean±SD, P<0.05), 5, and 10 minutes after thrombin receptor activator stimulation of whole blood to the same extent as anti-P-selectin (50 µg/mL; 288±177 MFI, P<0.05) when determined by flow cytometry. In parallel, the expression of the platelet activation marker P-selectin colocalized with CD14+ monocytes was reduced up to 25% by abciximab at the same time points. Expression of monocyte TF antigen (CD14+/TF+, 39.9±8.7% versus 66.3±19.9%, P<0.05), chromogenic TF-activity (TF, 8.4±1.9 versus 13.2±2.8 U, arbitrary units, P<0.05), and TF mRNA was suppressed in the presence of abciximab as a consequence of reduced platelet mass attached to monocytes.
Conclusions--Our data suggest that heterotypic monocyte-platelet aggregates are a target for abciximab, which suppresses monocyte TF because of a reduction of monocyte-platelet cross talk.
Key words: tissue factor • glycoprotein IIb/IIIa inhibition • abciximab • monocyte-platelet aggregates • flow cytometry
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