Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis?
Platelets release thrombopoietin (Tpo) upon activation: another regulatory loop in thrombocytopoiesis?
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DOI：
10.1055/s-0037-1613944
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发表时间：
2000-06-01
影响因子：
6.7
通讯作者：
von dem Borne, AEGK
中科院分区：
文献类型：
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作者：
Folman, CC;Linthorst, GE;von dem Borne, AEGK
血小板生成素由肝脏和肾脏以恒定速率产生，并在结合后通过血小板和巨核细胞表达的Tpo受体c-Mpl从循环中除去。本研究表明，血小板除了摄取Tpo外，还可以作为Tpo的储存库，在各种血小板激动剂的刺激下，血小板可释放具有生物活性的全长Tpo。血小板分级实验表明，这种Tpo最有可能包含在颗粒中。当血小板与TPO肽模拟物或截短的TPO最大活化前预孵育时，看到TPO释放增加3 - 5倍，而其他颗粒蛋白质如vWF-前肽或5-羟色胺的释放保持不变。因此，Mpl激动剂可能与Mpl结合的Tpo竞争，从而将Tpo释放到血小板上清液中。血小板的Tpo血管内释放可能发生在大量血小板活化的患者中，如发生在弥漫性血管内凝血的患者中。这些患者的Tpo浓度升高（p
Thrombopoietin is produced at a constant rate by the liver and kidney and is removed from the circulation upon binding and subsequent uptake via the Tpo receptor, c-Mpl, expressed by platelets and megakaryocytes. Apart from uptake, this study shows that platelets can also function as a storage pool for Tpo.Upon stimulation with various platelet agonists, full-length biologically active Tpo was released by platelets. Platelet fractionation experiments indicated that this Tpo most likely is contained in the granules. When platelets were preincubated with Tpo-peptide mimetic or truncated Tpo prior to maximal activation, a three- to fivefold increment in Tpo release was seen, whereas, the release of other granule proteins such as vWF-propeptide or serotonin remained unchanged. Therefore, the Mpl agonists might compete with Mpl-bound Tpo, thereby releasing Tpo into the platelet supernatant.Intravascular release of Tpo by platelets might occur in patients with massive platelet activation, as occurs in patients with disseminated intravascular coagulation. The Tpo concentration in these patients is elevated (p