Young thrombocytes initiate the formation of arterial thrombi in zebrafish
Young thrombocytes initiate the formation of arterial thrombi in zebrafish
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DOI：
10.1182/blood-2004-10-4118
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发表时间：
2005-07-01
期刊：
影响因子：
20.3
通讯作者：
Jagadeeswaran, P
中科院分区：
文献类型：
--
作者：
Thattaliyath, B;Cykowski, M;Jagadeeswaran, P
斑马鱼系统是研究止血和血栓形成的优良脊椎动物遗传模型，因为饱和诱变筛选可以鉴定在这一重要生理途径中发挥作用的新基因。为了研究止血突变，重要的是要了解斑马鱼止血和血栓形成的生理学。以前，我们确定了斑马鱼血小板，并表明它们参与动脉血栓形成。在这里，我们通过Dil-C18（Dil）染色识别出2个可区分的血小板群。Dil（+）血小板具有高密度的粘附受体，并且在功能上比Dil（-）血小板更活跃。我们将Dil（+）血小板分类为年轻血小板，Dil-血小板分类为成熟血小板。我们发现年轻的和成熟的血小板各自形成独立的簇，年轻的血小板首先聚集。我们还发现，年轻的血小板启动动脉血栓形成。我们认为，由于年轻血小板上的粘附受体密度增加，它们首先粘附到内皮下基质，迅速激活，释放激动剂，并招募更多的年轻血小板，从而进一步释放更多的激动剂。这种激动剂的增加激活了活性较低的成熟血小板，将它们吸引到正在生长的血栓中。由于动脉血栓形成是一个基本的止血事件，这种机制可能是保守的哺乳动物，并可能开辟新的途径，预防动脉血栓形成。
The zebrafish system is an excellent vertebrate genetic model to study hemostasis and thrombosis because saturation mutagenesis screens can identify novel genes that play a role in this vital physiologic pathway. To study hemostatic mutations, it is important to understand the physiology of zebrafish hemostasis and thrombosis. Previously, we identified zebrafish thrombocytes and have shown that they participate in arterial thrombus formation. Here, we recognized 2 populations of thrombocytes distinguishable by Dil-C18 (Dil) staining. Dil(+) thrombocytes have a high density of adhesive receptors and are functionally more active than Dil(-) thrombocytes. We classified Dil(+) thrombocytes as young and Dil- thrombocytes as mature thrombocytes. We found young and mature thrombocytes each formed independent clusters and that young thrombocytes clustered first. We have also shown that young thrombocytes initiate arterial thrombus formation. We propose that due to the increased adhesive receptor density on young thrombocytes, they adhere first to the subendothelial matrix, get activated rapidly, release agonists, and recruit more young thrombocytes, which further release more agonists. This increase in agonists; activates the less active mature thrombocytes, drawing them to the growing thrombus. Since arterial thrombus formation is a fundamental hemostatic event, this mechanism may be conserved in mammals and may open new avenues for prevention of arterial thrombosis.