Novel mechanisms of platelet clearance and thrombopoietin regulation.
Novel mechanisms of platelet clearance and thrombopoietin regulation.
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DOI：
10.1097/moh.0000000000000170
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发表时间：
2015-09
影响因子：
3.2
通讯作者：
Hoffmeister KM
中科院分区：
文献类型：
--
作者：
Grozovsky R;Giannini S;Falet H;Hoffmeister KM
人体每天产生并清除1011个血小板，以维持正常的稳态血小板计数。血小板的产生必须严格控制，以避免自发性出血或动脉闭塞和器官损伤。在生理和病理条件下，多方面和复杂的机制控制血小板的去除和产生。本文就血小板清除的不同机制作一综述，重点介绍血小板聚糖的生物学意义。Ashwell-Morrell受体（AMR）在稳态条件下识别衰老的去唾液酸化血小板。去唾液酸血小板和AMR是调节肝脏血小板生成素（TPO）mRNA产生的生理配体-受体对，解决了长期存在的稳态TPO调节之谜。AMR介导的去唾液酸化血小板的去除通过募集JAK 2和STAT 3来增加血小板生成来调节肝脏中的TPO合成。抑制肝脏AMR-JAK 2信号级联下游的TPO产生可能另外导致与JAK 1/2治疗相关的血小板减少症，JAK 1/2治疗在临床上用于骨髓增生性肿瘤。
The human body produces and removes 1011 platelets daily to maintain a normal steady-state platelet count. Platelet production must be tightly regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet removal and production in physiological and pathological conditions. This review will focus on different mechanisms of platelet clearance, with focus on the biological significance of platelet glycans. The Ashwell-Morrell receptor (AMR) recognizes senescent, desialylated platelets under steady state conditions. Desialylated platelets and the AMR are the physiological ligand-receptor pair regulating hepatic thrombopoietin (TPO) mRNA production, resolving the longstanding mystery of steady state TPO regulation. The AMR-mediated removal of desialylated platelets regulates TPO synthesis in the liver by recruiting JAK2 and STAT3 to increase thrombopoiesis. Inhibition of TPO production downstream of the hepatic AMR-JAK2 signaling cascade could additionally contribute to the thrombocytopenia associated with JAK1/2 treatment, which is clinically used in myeloproliferative neoplasms.