PMID- 12855480 OWN - NLM STAT- MEDLINE DCOM- 20040204 LR - 20061115 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 23 IP - 9 DP - 2003 Sep 1 TI - Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs. PG - 1690-6 AB - 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. FAU - Camera, Marina AU - Camera M AD - Department of Pharmacological Sciences, University of Milan, Italy. FAU - Frigerio, Marta AU - Frigerio M FAU - Toschi, Vincenzo AU - Toschi V FAU - Brambilla, Marta AU - Brambilla M FAU - Rossi, Francesca AU - Rossi F FAU - Cottell, David C AU - Cottell DC FAU - Maderna, Paola AU - Maderna P FAU - Parolari, Alessandro AU - Parolari A FAU - Bonzi, Roberto AU - Bonzi R FAU - De Vincenti, Ombretta AU - De Vincenti O FAU - Tremoli, Elena AU - Tremoli E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20030710 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Antigens, Surface) RN - 0 (Platelet Aggregation Inhibitors) RN - 0 (RNA, Messenger) RN - 9035-58-9 (Thromboplastin) SB - IM MH - Antigens, Surface/*biosynthesis/immunology/*metabolism/physiology MH - Blood Platelets/chemistry/drug effects/ultrastructure MH - Humans MH - Microscopy, Electron/methods MH - Platelet Activation/*drug effects/*physiology MH - Platelet Aggregation Inhibitors/*pharmacology MH - RNA, Messenger/metabolism MH - Thromboplastin/*biosynthesis/immunology/*metabolism/physiology EDAT- 2003/07/12 05:00 MHDA- 2004/02/05 05:00 CRDT- 2003/07/12 05:00 PHST- 2003/07/12 05:00 [pubmed] PHST- 2004/02/05 05:00 [medline] PHST- 2003/07/12 05:00 [entrez] AID - 01.ATV.0000085629.23209.AA [pii] AID - 10.1161/01.ATV.0000085629.23209.AA [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2003 Sep 1;23(9):1690-6. doi: 10.1161/01.ATV.0000085629.23209.AA. Epub 2003 Jul 10.