Published online before print July 10, 2003, doi: 10.1161/01.ATV.0000085629.23209.AA
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© 2003 American Heart Association, Inc.
Thrombosis |
Platelet Activation Induces Cell-Surface Immunoreactive Tissue Factor Expression, Which Is Modulated Differently by Antiplatelet Drugs
From the Department of Pharmacological Sciences (M.C., M.B., O.D.V., E.T.), University of Milan; Monzino Cardiologic Center IRCCS (M.C., M.F., F.R., A.P., R.B., E.T.); and the Department of Hematology and Blood Transfusion (V.T.), San Carlo Borromeo Hospital, Milan, Italy; and the Electron Microscopy Laboratory (D.C.C.) and Conway Institute of Biomolecular and Biomedical Research (P.M.), University College Dublin, Dublin, Ireland.
Correspondence to Elena Tremoli, Department of Pharmacological Sciences, University of Milan, Via Balzaretti, 9, 20133 Milan, Italy. E-mail Elena.Tremoli{at}unimi.it
Objective— Tissue factor (TF) is the main activator of the coagulation cascade occurring in physiologic and pathologic conditions. Recent data suggest that human platelets might contain TF that is possibly derived from leukocytes. In this study, we investigated whether intraplatelet TF can be exposed on the membrane by platelet agonists. The modulation of this process by antiplatelet drugs has been evaluated as well.
Methods and Results— Flow cytometric analysis of unstimulated platelets showed a small amount of membrane-associated immunoreactive TF (irTF) in whole blood, platelet-rich plasma, and washed platelets isolated from healthy subjects. ADP, thrombin receptor-activating peptide, and epinephrine significantly increased functionally active, membrane-associated irTF. ADP induced irTF exposure in a concentration- and time-dependent fashion. Agonist-induced irTF expression was completely inhibited by iloprost but not by aspirin. Interestingly, glycoprotein IIb/IIIa antagonists did not inhibit but rather potentiated the stimulatory effect of ADP on platelet irTF expression. Real-time polymerase chain reaction experiments showed detectable amounts of TF mRNA in unstimulated platelets.
Conclusions— These findings indicate that platelet agonists and antiplatelet drugs might modulate platelet-associated irTF expression. Regulated TF expression establishes the potential for a previously unrecognized role for platelets in sustaining thrombus formation and growth via coagulation-mediated mechanisms.
Key Words: platelets • tissue factor • coagulation • thrombosis • antiplatelet agents
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