Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs

Marina Camera, Marta Frigerio, Vincenzo Toschi, Marta Brambilla, Francesca Rossi, David C. Cottell, Paola Maderna, Alessandro Parolari, Roberto Bonzi, Ombretta De Vincenti, Elena Tremoli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1690-1696
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume23
Issue number9
DOIs
Publication statusPublished - Sep 1 2003

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Platelet Aggregation Inhibitors
Platelet Activation
Thromboplastin
Blood Platelets
Adenosine Diphosphate
thrombin receptor peptide SFLLRNP
Membranes
Iloprost
Platelet Glycoprotein GPIIb-IIIa Complex
Platelet-Rich Plasma
Epinephrine
Aspirin
Real-Time Polymerase Chain Reaction
Healthy Volunteers
Thrombosis
Leukocytes
Messenger RNA

Keywords

  • Antiplatelet agents
  • Coagulation
  • Platelets
  • Thrombosis
  • Tissue factor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs. / Camera, Marina; Frigerio, Marta; Toschi, Vincenzo; Brambilla, Marta; Rossi, Francesca; Cottell, David C.; Maderna, Paola; Parolari, Alessandro; Bonzi, Roberto; De Vincenti, Ombretta; Tremoli, Elena.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 9, 01.09.2003, p. 1690-1696.

Research output: Contribution to journalArticle

Camera, Marina ; Frigerio, Marta ; Toschi, Vincenzo ; Brambilla, Marta ; Rossi, Francesca ; Cottell, David C. ; Maderna, Paola ; Parolari, Alessandro ; Bonzi, Roberto ; De Vincenti, Ombretta ; Tremoli, Elena. / Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 ; Vol. 23, No. 9. pp. 1690-1696.
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AU - Cottell, David C.

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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.

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