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Title: Characterisation and studies of T-lymphoblastoid procoagulant activity
Author: Pickering, William Maxwell
ISNI:       0000 0001 3490 0363
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2004
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Coagulation is an interaction between tissue factor (TF) and clotting factors, assembled on a negatively-charged phospholipid surface. Previously it was reported that malignant T-lymphoblastoid cells might have the ability to support procoagulant activity (PCA). In the present study human T-cell lines (CEM-CCRF, Jurkat, Molt-4, A3.01) representing different stages of differentiation were cultured and their basal PCA compared with that of a monocytoid cell line (THP-1). Various phospholipid or TF-dependent coagulation tests were used to investigate this PCA. The effect of TF on the phospholipid-dependent assays was also investigated.;The phospholipid dependent PCA was reported as phospholipid units/mL by comparison with a bovine brain phospholipid standard. There was variation in the procoagulant activity between the cell lines. Using calcium ionophore to stimulate this activity, and annexin A5 and an inhibitory phosphatidylserine antibody (3G4) to inhibit it, along with flow cytometry data, it was concluded that this activity was due to the exposure of anionic phospholipid.;Two pathophysiological processes, apoptosis and lipid peroxidation significantly enhanced the PCA of T-Lymphoblastoid cells. This enhanced PCA was higher than that observed following calcium ionophore treatment, suggesting the increase in activity was not solely due to anionic phospholipid exposure. Whilst annexin A5FITC and 3G4 bound to cells undergoing apoptosis only annexin A5FITC bound to cells exposed to oxidative stress. This implies that apoptosis increases PCA by causing the translocation of oxidised/native phosphatidylserine to the outer membrane, whilst lipid peroxidation appears to increase the PCA possibly due to malondialdehyde-adducts altering the net charge on the cell surface, which allows phospholipids other than phosphatidylserine to participate in thrombin generation. The possible pathophysiological significance of these observations with regard to thromboembolic complications of leukaemia, chemotherapy and atherosclerosis is discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available