1. Expression of functional tissue factor in activated T-lymphocytes in vitro and in vivo: A possible contribution of immunity to thrombosis?
- Author
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Plinio Cirillo, Giuseppe Pasquale, Giovanni Ciccarelli, Gaetano Calì, Grazia Pellegrino, Stefano Conte, Francesco Pacifico, Paolo Golino, Giovanni Cimmino, Giusi Barra, Raffaele De Palma, Giovanni Nassa, Antonio Leonardi, Luigi Insabato, DE PALMA, Raffaele, Plinio, Cirillo, Giovanni, Ciccarelli, Giusi, Barra, Stefano, Conte, Grazia, Pellegrino, Giuseppe, Pasquale, Giovanni, Nassa, Francesco, Pacifico, Antonio, Leonardi, Lucio, Insabato, Guido, Calì, Golino, Paolo, Cimmino, Giovanni, De Palma, Raffaele, Cirillo, Plinio, Ciccarelli, Giovanni, Barra, Giusi, Conte, Stefano, Pellegrino, Grazia, Pasquale, Giuseppe, Nassa, Giovanni, Pacifico, FRANCESCO MARIA, Leonardi, Antonio, Insabato, Luigi, and Calì, Gaetano
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,T-lymphocyte ,T-Lymphocytes ,CD3 ,Inflammation ,Atherosclerosis ,Thrombosis ,Tissue factor ,Cardiology and Cardiovascular Medicine ,In Vitro Techniques ,030204 cardiovascular system & hematology ,Coronary Angiography ,Lymphocyte Activation ,Thromboplastin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,Humans ,Medicine ,Acute Coronary Syndrome ,Cells, Cultured ,Aged ,biology ,business.industry ,CD28 ,Middle Aged ,Molecular biology ,In vitro ,030104 developmental biology ,chemistry ,Atherosclerosi ,Ionomycin ,Thrombosi ,biology.protein ,Female ,medicine.symptom ,business ,Signal Transduction - Abstract
Objective T-lymphocyte activation plays an important role in the pathophysiology of acute coronary syndromes (ACS). Plaques from ACS patients show a selective oligoclonal expansion of T-cells, indicating a specific, antigen-driven recruitment of T-lymphocytes within the unstable lesions. At present, however, it is not known whether T-cells may contribute directly to thrombosis by expressing functional tissue factor (TF). Accordingly, the aim of the present study was to investigate whether T-cells are able to express functional TF in their activated status. Methods In vitro , CD3 + -cells, isolated from buffy coats, were stimulated with anti-CD3/CD28 beads, IL-6, TNF-α, IL-17, INF-γ or PMA/ionomycin. Following stimulation, TF expression on cell-surface, at gene and protein levels, as well as its procoagulant activity in whole cells and microparticles was measured. In vivo , TF expression was evaluated in CD3 + -cells isolated from the aorta and the coronary sinus of ACS-NSTEMI and stable coronary artery disease (SCAD) patients. The presence of CD3 + -TF + cells was also evaluated by immunohistochemistry in thrombi aspirated from ACS-STEMI patients. Results PMA/ionomycin and IL-17 plus INF-γ stimulation resulted in a significant TF increase at gene and protein levels as well as at cell-surface expression. This was accompanied by a parallel increase in FXa generation, both in whole cells and in microparticles, indicating that the induced membrane-bound TF was active. Furthermore, transcardiac TF gradient was significantly higher in CD3 + -cells obtained from ACS-patients compared to SCAD-patients. Interestingly, thrombi from ACS-STEMI patients resulted enriched in CD3 + -cells, most of them expressing TF. Conclusions Our data demonstrate that activated T-lymphocytes in vitro express functional TF on their membranes, suggesting a direct pathophysiological role of these cells in the thrombotic process; this hypothesis is further supported by the observations in vivo that CD3 + -cells from coronary circulation of ACS-NSTEMI patients show increased TF levels and that coronary thrombi from ACS-STEMI patients are enriched in CD3 + -cells expressing TF.
- Published
- 2016
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