Kuter D J, Rosenberg R D
Department of Biology, Massachusetts Institute of Technology, Cambridge, USA.
Blood. 1995 May 15;85(10):2720-30.
Thrombopoietin (c-Mpl ligand) has recently been purified and is considered to be the humoral regulator of platelet production. To see whether this molecule possessed the physiologic characteristics necessary to mediate the feed-back loop between blood platelets and the bone marrow megakaryocytes, we determined the relationship between blood levels of thrombopoietin and changes in the circulating platelet mass. We developed a model of nonimmune thrombocytopenia in rabbits by the subcutaneous administration of busulfan. Compared with pretreatment plasma, plasma taken from all thrombocytopenic rabbits at their platelet nadir contained increased amounts of thrombopoietin. All of this activity was neutralized by soluble c-Mpl receptor. We subsequently measured the level of thrombopoietin in the circulation over the entire time course after the administration of busulfan. As the platelet mass declined, levels of thrombopoietin increased inversely and proportionally and peaked during the platelet nadir. With return of the platelet mass toward normal, thrombopoietin levels decreased accordingly. When platelets were transfused into thrombocytopenic rabbits near the time of their platelet count nadir, the elevated levels of thrombopoietin decreased. In addition, platelets were observed to remove thrombopoietin from thrombocytopenic plasma in vitro. These results confirm that thrombopoietin is the humoral mediator of megakaryocytopoiesis and suggest that the platelet mass may directly play a role in regulating the circulating levels of this factor.
血小板生成素（c-Mpl配体）最近已被纯化，并被认为是血小板生成的体液调节因子。为了探究该分子是否具备介导血小板与骨髓巨核细胞之间反馈回路所需的生理特性，我们测定了血小板生成素的血药浓度与循环血小板量变化之间的关系。我们通过皮下注射白消安建立了兔非免疫性血小板减少症模型。与预处理血浆相比，所有血小板减少症兔在血小板计数最低点时采集的血浆中血小板生成素含量增加。所有这些活性均被可溶性c-Mpl受体中和。随后，我们在注射白消安后的整个时间过程中测量了循环中血小板生成素的水平。随着血小板量下降，血小板生成素水平呈反比且成比例增加，并在血小板计数最低点时达到峰值。随着血小板量恢复正常，血小板生成素水平相应下降。当在血小板计数最低点附近给血小板减少症兔输注血小板时，升高的血小板生成素水平降低。此外，在体外观察到血小板可从血小板减少症血浆中清除血小板生成素。这些结果证实血小板生成素是巨核细胞生成的体液介质，并表明血小板量可能直接参与调节该因子的循环水平。
