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P-selectin - a novel protein in hemostasis
Hrachovinová, Ingrid ; Brdička, Radim (advisor) ; Kvasnička, Jan (referee) ; Penka, Miroslav (referee)
Originally, P-selectin played an important role in the vascular response to inflammation. In the first half of the nineties there were published papers demonstrated that P-selectin also played a significant role in blood coagulation and thrombosis. In these experiments anti-P-selectin antibodies blocked fibrin formation and suppressed the developing of thrombus. Shortly thereafter, P-selectin was shown to upregulate tissue factor (TF) generation on monocytes. The active role of P-selectin in hemostasis was supported also with our findings that overexpression of soluble P-selectin (sP-sel) can induce a procoagulant state in plasma/blood. I have focused in my postgraduate study on pathophysiology of sP-sel , its role in formation of microparicles (MPs) bearing TF. In the detail study of sP-sel we found, that procoagulant state in plasma is due to procoagulant MPs, part of them contained TF. We confirmed that recently characterized "blood-borne" TF could be induced by sP-sel. Moreover, because the production of microparticles was suppressed by inhibiting antibody against PSGL-1 (receptor of P-selectin on leukocytes), we proposed the origin of MPs from leukocytes. Recruitment of TF-bearing MPs from monocytes I demonstrated later with FACS screening of presence of specific CD-markers. I realized that...
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