Mer receptor tyrosine kinase signaling participates in platelet function
Mer receptor tyrosine kinase signaling participates in platelet function
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DOI：
10.1161/01.atv.0000130662.30537.08
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发表时间：
2004-06-01
影响因子：
8.7
通讯作者：
Damiano, BP
中科院分区：
文献类型：
--
作者：
Chen, CL;Li, Q;Damiano, BP
目的：最近，生长停滞特异性基因6产物（Gas 6）缺陷或Gas 6基因表达被抑制的小鼠显示出血小板功能障碍，并且对血栓形成不太敏感。本研究的目的是定义和表征相关的Gas 6受体或受体参与血小板function.Methods和结果-使用RT-PCR和Western blot分析，我们发现，mer是主要表达的亚型在小鼠和人的血小板，而axl和rse没有检测到。我们通过靶向破坏mer受体基因产生mer缺陷小鼠。来自mer缺陷小鼠的血小板在体外对低浓度胶原、U46619和PAR 4凝血酶受体激动剂肽的反应中具有降低的血小板聚集。然而，对ADP的反应与野生型血小板没有区别。mer基因的敲除保护小鼠免受胶原/肾上腺素诱导的肺血栓栓塞，并抑制氯化铁诱导的体内血栓形成。尾部出血时间，凝血参数，和外周血细胞计数在mer缺陷的小鼠是类似的野生型mice.Conclusion -我们的数据提供了第一个证据，mer，大概是通过激活其配体Gas 6，参与调节血小板功能在体外和血小板依赖性血栓形成在体内。
Objective - Recently, mice made deficient in growth arrest - specific gene 6 product (Gas6) or in which Gas6 gene expression was inhibited were shown to have platelet dysfunction and to be less susceptible to thrombosis. The aim of this study was to define and characterize the relevant Gas6 receptor or receptors involved in platelet function.Methods and Results - Using RT-PCR and Western blot analysis we found that mer was the predominantly expressed subtype in mouse and human platelets, whereas axl and rse were not detected. We generated mer-deficient mice by targeted disruption of the mer receptor gene. Platelets derived from mer-deficient mice had decreased platelet aggregation in responses to low concentrations of collagen, U46619, and PAR4 thrombin receptor agonist peptide in vitro. However, the response to ADP was not different from wild-type platelets. Knockout of the mer gene protected mice from collagen/epinephrine- induced pulmonary thromoembolism and inhibited ferric chloride - induced thrombosis in vivo. Tail bleeding times, coagulation parameters, and peripheral blood cell counts in mer-deficient mice were similar to wild-type mice.Conclusion - Our data provide the first evidence that mer, presumably through activation by its ligand Gas6, participates in regulation of platelet function in vitro and platelet-dependent thrombosis in vivo.