Role of Young Thrombocytes and Their Microparticles

University Of Texas Hlth Sci Ctr San Ant, San Antonio TX

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Abstract

DESCRIPTION (provided by applicant): 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.