Platelets are important players in hemostasis and thrombosis. In mammals, there are two types of platelets, namely young and mature, that carry greater and less numbers of adhesive receptors respectively. Platelets produce microparticles and also carry these receptors. Despite decades of work in hemostasis and thrombosis, the in vivo function of neither young platelets nor their microparticles, is known. Zebrafish is an excellent model system to delineate functions of young platelets and their microparticles since they possess platelet equivalents called thrombocytes. In our preliminary studies, we have shown young thrombocytes are more active, carry more receptors and appear at the wounding site first in the zebrafish arterial injury model. Likewise, we have identified similar receptors on circulating thrombocyte microparticles. Since young thrombocytes are more active, it is possible that they subsequently generate more active microparticles. These microparticles may be first ones to participate in the adhesive reaction because there is a greater likelihood of finding the smaller-sized components at or near the vessel wall in flowing blood. Furthermore, it is likely that by microvesicular shedding young thrombocytes may lose the receptors and become less active mature thrombocytes. Thus, our hypothesis is that young thrombocytes generate microparticles by an unknown mechanism, lose their receptors as micro vesicles to become less active mature thrombocytes, and these microparticles generated in turn may help in the initiation of the thrombus along with young thrombocytes. In this grant application, we propose to establish the selective recruitment of microparticles and young thrombocytes to the wounding site in zebrafish and use the power of zebrafish genetics to isolate and characterize zebrafish mutants with defects in microparticle shedding. Such studies should provide insight into the role of platelet microparticles in hemostasis, mechanisms of their production and platelet maturation.
| Kim, Seongcheol; Sundaramoorthi, Hemalatha; Jagadeeswaran, Pudur (2015) Dioxin-induced thrombocyte aggregation in zebrafish. Blood Cells Mol Dis 54:116-22 |
| Kulkarni, Vrinda; Kim, Seongcheol; Zafreen, Lala et al. (2012) Separation of young and mature thrombocytes by a novel immuno-selection method. Blood Cells Mol Dis 48:183-7 |
| Kim, Seongcheol; Carrillo, Maira; Radhakrishnan, Uvaraj P et al. (2012) Role of zebrafish thrombocyte and non-thrombocyte microparticles in hemostasis. Blood Cells Mol Dis 48:188-96 |
| Hughes, Craig E; Radhakrishnan, Uvaraj P; Lordkipanidzé, Marie et al. (2012) G6f-like is an ITAM-containing collagen receptor in thrombocytes. PLoS One 7:e52622 |
| Kim, Seongcheol; Radhakrishnan, Uvaraj P; Rajpurohit, Surendra Kumar et al. (2010) Vivo-Morpholino knockdown of alphaIIb: A novel approach to inhibit thrombocyte function in adult zebrafish. Blood Cells Mol Dis 44:169-74 |
| Carrillo, Maira; Kim, Seongcheol; Rajpurohit, Surendra Kumar et al. (2010) Zebrafish von Willebrand factor. Blood Cells Mol Dis 45:326-33 |
| Jagadeeswaran, Pudur; Lin, Shuo; Weinstein, Brant et al. (2010) Loss of GATA1 and gain of FLI1 expression during thrombocyte maturation. Blood Cells Mol Dis 44:175-80 |
| Kim, Seongcheol; Carrillo, Maira; Kulkarni, Vrinda et al. (2009) Evolution of primary hemostasis in early vertebrates. PLoS One 4:e8403 |
| Kim, Seongcheol; Carlson, Ryan; Zafreen, Lala et al. (2009) Modular, easy-to-assemble, low-cost zebrafish facility. Zebrafish 6:269-74 |
| Day, Kenneth R; Jagadeeswaran, Pudur (2009) Microarray analysis of prothrombin knockdown in zebrafish. Blood Cells Mol Dis 43:202-10 |
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