Thrombogenic role of cells undergoing apoptosis.
Apoptosis is involved in many biological processes, especially during chemotherapy in cancer patients. Chemotherapy is also associated with an increased risk of thrombosis. The relationship between thrombogenicity and apoptosis was studied in various human tumour cell lines and non-tumour cell lines. Apoptosis was induced by the chemotherapeutic agent camptothecin and by Fas ligand, then quantified by staining with fluorescein isothiocyanate-conjugated annexin V and propidium iodide. A significant correlation between thrombin generation and degree of apoptosis was observed (P < 0.0005). Addition of anti-tissue factor antibody in excess or of tissue factor pathway inhibitor partially inhibited thrombin generation, suggesting that tissue factor activation was responsible for this process. A statistical correlation between tissue factor activity and degree of apoptosis was also found (P < 0.005). Both thrombin generation and tissue factor activity were blocked by the addition of annexin V, which binds and inhibits phosphatidylserine. This indicates that the exteriorization and exposure of phosphatidylserine on the cell surface membrane during apoptosis were essential for both thrombin generation and tissue factor activation.
Wang
J
J
Division of Hematology/Oncology, Department of Medicine, Northwestern University Medical School, Chicago, IL, USA.
Weiss
I
I
Svoboda
K
K
Kwaan
H C
HC
D017304:Annexin A5 / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002166:Camptothecin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010718:Phosphatidylserines / Q000037:antagonists & inhibitors / Q000502:physiology; D013917:Thrombin / Q000096:biosynthesis*; D013925:Thromboplastin / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D010718:Phosphatidylserines; D013925:Thromboplastin; D013917:Thrombin; D002166:Camptothecin