Department of Clinical Pathophysiology, University of Turin, via Genova 3, 10126 Turin, Italy.
Mediators Inflamm. 2012;2012:390892. doi: 10.1155/2012/390892. Epub 2012 Apr 5.
Thrombopoietin (TPO) is a humoral growth factor originally identified for its ability to stimulate the proliferation and differentiation of megakaryocytes. In addition to its actions on thrombopoiesis, TPO directly modulates the homeostatic potential of mature platelets by influencing their response to several stimuli. In particular, TPO does not induce platelet aggregation per se but is able to enhance platelet aggregation in response to different agonists ("priming effect"). Our research group was actively involved, in the last years, in characterizing the effects of TPO in several human critical diseases. In particular, we found that TPO enhances platelet activation and monocyte-platelet interaction in patients with unstable angina, chronic cigarette smokers, and patients with burn injury and burn injury complicated with sepsis. Moreover, we showed that TPO negatively modulates myocardial contractility by stimulating its receptor c-Mpl on cardiomyocytes and the subsequent production of NO, and it mediates the cardiodepressant activity exerted in vitro by serum of septic shock patients by cooperating with TNF-α and IL-1β. This paper will summarize the most recent results obtained by our research group on the pathogenic role of elevated TPO levels in these diseases and discuss them together with other recently published important studies on this topic.
血小板生成素（TPO）是一种体液生长因子，最初因其能够刺激巨核细胞的增殖和分化而被识别。除了对造血的作用外，TPO 还通过影响成熟血小板对几种刺激物的反应，直接调节其体内平衡潜力。特别是，TPO 本身不会诱导血小板聚集，但能够增强对不同激动剂的血小板聚集反应（“预刺激效应”）。在过去的几年中，我们的研究小组积极参与了表征 TPO 在几种人类危急疾病中的作用。特别是，我们发现 TPO 增强了不稳定型心绞痛、慢性吸烟者、烧伤患者和烧伤合并脓毒症患者的血小板激活和单核细胞-血小板相互作用。此外，我们还表明，TPO 通过刺激心肌细胞上的受体 c-Mpl 及其随后产生的 NO 来负调节心肌收缩力，并通过与 TNF-α 和 IL-1β 合作，介导脓毒症休克患者血清在体外发挥的心脏抑制活性。本文将总结我们研究小组在这些疾病中升高的 TPO 水平的致病作用方面获得的最新结果，并与该主题的其他最近发表的重要研究一起进行讨论。
