Platelet Activation Induces Cell-Surface Immunoreactive Tissue Factor Expression, Which Is Modulated Differently by Antiplatelet Drugs
- 1 September 2003
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 23 (9), 1690-1696
- https://doi.org/10.1161/01.atv.0000085629.23209.aa
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.Keywords
This publication has 14 references indexed in Scilit:
- Platelet Glycoprotein IIb/IIIa InhibitorsCirculation, 2002
- Activated platelets mediate inflammatory signaling by regulated interleukin 1β synthesisThe Journal of cell biology, 2001
- Platelet-Associated Tissue Factor Contributes to the Collagen-Triggered Activation of Blood CoagulationBiochemical and Biophysical Research Communications, 2001
- Tissue Factor, the Blood, and the Arterial WallTrends in Cardiovascular Medicine, 2000
- Factor XI Messenger RNA in Human PlateletsBlood, 1999
- Blood-borne tissue factor: Another view of thrombosisProceedings of the National Academy of Sciences of the United States of America, 1999
- Tissue-factor antigen and activity in human coronary atherosclerotic plaquesThe Lancet, 1997
- Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque.Proceedings of the National Academy of Sciences of the United States of America, 1989
- Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extractionAnalytical Biochemistry, 1987
- Albumin Density Gradient Separation and Washing of Platelets and the Study of Platelet Coagulant ActivitiesBritish Journal of Haematology, 1972