Kaushansky K, Broudy V C, Grossmann A, Humes J, Lin N, Ren H P, Bailey M C, Papayannopoulou T, Forstrom J W, Sprugel K H
Division of Hematology, University of Washington, Seattle 98195, USA.
J Clin Invest. 1995 Sep;96(3):1683-7. doi: 10.1172/JCI118210.
Thrombopoietin (TPO), the ligand for the receptor protooncogene c-mpl, has been cloned and shown to be the critical regulator of platelet production. Several features of c-Mpl expression, including its presence on erythroid cell lines, and the panmyeloid transformation characteristic of myeloproliferative leukemia (MPL) viral disease led us to investigate whether this receptor-ligand system may play a role in erythropoiesis. We report that although TPO alone did not support the growth of either early or late erythroid progenitors, it acted in synergy with erythropoietin to expand these populations. Moreover, while the effects on erythropoiesis in normal animals were modest, TPO greatly expanded the number of erythroid progenitors and blood reticulocytes and was associated with accelerated red cell recovery in myelosuppressed mice. Together, these data strongly suggest that erythroid progenitors respond to TOP and that this newly cloned cytokine, critical for platelet production, can augment erythropoiesis in states of marrow failure.
血小板生成素（TPO）是原癌基因c-mpl受体的配体，已被克隆出来，并被证明是血小板生成的关键调节因子。c-Mpl表达的几个特征，包括其在红系细胞系上的存在，以及骨髓增殖性白血病（MPL）病毒疾病的全髓系转化特征，促使我们研究这种受体-配体系统是否可能在红细胞生成中发挥作用。我们报告，虽然单独的TPO不支持早期或晚期红系祖细胞的生长，但它与促红细胞生成素协同作用以扩大这些细胞群体。此外，虽然对正常动物红细胞生成的影响不大，但TPO大大增加了红系祖细胞和血液中网织红细胞的数量，并与骨髓抑制小鼠红细胞的加速恢复有关。总之，这些数据强烈表明红系祖细胞对TPO有反应，并且这种新克隆的、对血小板生成至关重要的细胞因子可以在骨髓衰竭状态下增强红细胞生成。
