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 language | English |
|---|---|
| Pages (from-to) | 1690-1696 |
| Number of pages | 7 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 23 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sep 1 2003 |
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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 journal › Article
}
TY - JOUR
T1 - Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs
AU - Camera, Marina
AU - Frigerio, Marta
AU - Toschi, Vincenzo
AU - Brambilla, Marta
AU - Rossi, Francesca
AU - Cottell, David C.
AU - Maderna, Paola
AU - Parolari, Alessandro
AU - Bonzi, Roberto
AU - De Vincenti, Ombretta
AU - Tremoli, Elena
PY - 2003/9/1
Y1 - 2003/9/1
N2 - 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.
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.
KW - Antiplatelet agents
KW - Coagulation
KW - Platelets
KW - Thrombosis
KW - Tissue factor
UR - http://www.scopus.com/inward/record.url?scp=10744232582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744232582&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000085629.23209.AA
DO - 10.1161/01.ATV.0000085629.23209.AA
M3 - Article
C2 - 12855480
AN - SCOPUS:10744232582
VL - 23
SP - 1690
EP - 1696
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 9
ER -