The residual megakaryocyte and platelet production in c-Mpl-deficient mice is not dependent on the actions of interleukin-6, interleukin-11, or leukemia inhibitory factor

作     者：Gainsford, T Nandurkar, H Metcalf, D Robb, L Begley, CG Alexander, WS 

作者机构：Walter & Eliza Hall Inst Med Res Melbourne Vic 3050 Australia Royal Melbourne Hosp Cooperat Res Ctr Cellular Growth Factors Melbourne Vic Australia Royal Melbourne Hosp Rotary Bone Marrow Res Labs Melbourne Vic Australia 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第2期

页      面：528-534页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NCI NIH HHS [CA22556] Funding Source: Medline NHLBI NIH HHS [HL62275] Funding Source: Medline 

主　　题：血小板/细胞学 骨髓细胞/细胞学 基因型 生长抑制物/缺乏 生长抑制物/遗传学 生长抑制物/生理学 血细胞生成/遗传学 血细胞生成/生理学 造血干细胞/细胞学 造血干细胞/药物作用 造血干细胞/生理学 白细胞介素11/缺乏 白细胞介素11/遗传学 白细胞介素11/生理学 白细胞介素6/缺乏 白细胞介素6/遗传学 白细胞介素6/生理学 白血病抑制因子 淋巴因子/缺乏 淋巴因子/遗传学 淋巴因子/生理学 巨核细胞/细胞学 小鼠 基因敲除 肿瘤蛋白质类 血小板计数 原癌基因蛋白质类/缺乏 原癌基因蛋白质类/遗传学 原癌基因蛋白质类/生理学 受体 细胞因子 受体 血小板生成素 脾/细胞学 血小板生成素/缺乏 血小板生成素/遗传学 血小板生成素/生理学 动物 小鼠 

摘      要：Mice lacking thrombopoietin (TPO) or its receptor c-Mpl are severely thrombocytopenic, consistent with a dominant physiological role for this cytokine in megakaryocytopoiesis, However, these mice remain healthy and show no signs of spontaneous hemorrhage, implying that TPO-independent mechanisms for platelet production exist and are sufficient for hemostasis. To investigate the roles of cytokines that act through the gp130 signaling chain in the residual platelet production of mpl(-/-) mice, mpl -/-IL-6(-/-), mpl(-/-)LIF(-/-), and mpl(-/-)IL-11R alpha(-/-) double-mutant mice were generated. In each of these compound mutants, the number of circulating platelets was no lower than that observed in mice lacking only the c-mpl gene. Moreover, the deficits in the numbers of megakaryocytes and megakaryocyte progenitor cells in the bone marrow and spleen were no further exacerbated in mpl(-/-)L-6(-/-), mpl(-/-)LIF(-/-), or mpl(-/-) IL-11R alpha(-/-) double-mutant mice compared, with those in Mpl-deficient animals. In single IL-6(-/-), LIF-/-, and IL-11R alpha(-/-) mutant mice, platelet production was normal. These data establish that, as single regulators, IL-6, IL-11, and LIF have no essential role in normal steady-state megakaryocytopoiesis, and are not required for the residual megakaryocyte and platelet production seen in the c-mpl(-/-) mouse. (Blood, 2000;95:528-534) (C) 2000 by The American Society of Hematology.