Mathematical Biology Seminar Connie Hall Friday April 11, 2008 2:00pm in AEB 310 "Monocyte-derived Microparticles in Biomaterial Thrombogenicity" " Abstract: Thrombosis on biomaterials in contact blood remains an important concern. Recent evidence suggests a role for the extrinsic pathway of coagulation not previously considered. Blood-borne tissue factor (TF) bearing microparticles released from activated or apoptotic cells circulate in elevated numbers in a variety of disease states including myocardial infarction, diabetes, sickle cell disease, and trauma and following cardiopulmonary bypass. It has also been shown that TF bearing microparticles deposit in growing thrombi and increase fibrin deposition in the microcirculation of a mouse model of thrombosis. The transport and adhesion of model monocytic microparticles from THP-1 cells were therefore studied in in vitro flow systems. . Microparticle (MP) suspensions supported TF-dependent and independent activation of FX to FXa in the presence of FVIIa and calcium. Blood-borne tissue factor (TF) bearing microparticles adhered to artificial surfaces and imparted TF activity to the surface. MP suspensions were exposed to protein (fibrinogen, collagen, fibronectin) coated polystyrene (PS) at wall shear rates of 100 to 1550 sec-1 for one hour and the resulting TF activity of the surface was evaluated by measuring the activation of FX as an indicator of procoagulant activity. The activity imparted to fibrinogen coated PS increased with increasing wall shear rate from 100 to 1200 sec-1, whereas fibronectin and collagen surfaces did not exhibit shear rate dependence. MP deposition on PS was also visualized microscopically in the presence and absence of platelets showing co-localization with platelets. Flow cytometric analysis of MPs demonstrated the presence of the integrin CD11b/CD18, a receptor for fibrinogen, in addition to PSGL-1, a counter-receptor for P-selectin on activated platelets indicating the potential for specific interactions. Studies with inhibitory antibodies are in progress to definitively determine the nature of these interactions.