【科技前瞻】Nature子刊:血小板及其外泌体的那些事儿

栏目:365bet手机投注 来源:家具迷 时间:2019-04-12

血小板是主要由骨髓中的巨核细胞不断产生的血细胞,不仅涉及止血和动脉血栓形成,还涉及其他生理和病理过程。近日,研究人员综述了血小板结构异质性的现有证据,以及对血小板功能的影响。作为高反应性和分泌性细胞,血小板可通过释放生长因子、趋化因子、凝血因子、RNA和细胞外囊泡来改变环境和适应环境。在疾病状态下,血小板可以被诱导到预激活状态。在发炎的血管壁处,血小板与白细胞和凝血系统相互作用,介导血栓炎症。目前的抗血小板治疗总是导致出血的副作用,因此研究人员长期致力于针对特定的血小板反应、群体、相互作用或引发条件,开发靶向血小板治疗策略。

在过去十年中,越来越多研究关注了从血小板释放的膜囊泡,这些细胞外囊泡包含外泌体(直径40-100nm)和微泡(直径100-1000nm)。血液循环中的大多数囊泡是血小板或巨核细胞衍生的,外泌体在血液相关生理过程中发挥作用。通过血小板衍生的细胞外囊泡生物活性细胞因子,包括类二十烷酸、凝血因子和RNA的存在证实了这种作用,通过配体呈递和膜融合,这些囊泡和其他细胞之间还能够发生相互作用。血小板衍生的细胞外囊泡与白细胞的相互作用主要在炎症的背景下被报道。有趣的是,受血小板状态是衰老或激活,细胞外囊泡似乎在糖蛋白表达水平上有所不同,并且在调节单核细胞功能方面不同。研究人员在类风湿性关节炎中观察到血小板衍生的细胞外囊泡刺激滑膜成纤维细胞产生细胞因子。然而,目前人们对血小板衍生囊泡中的什么成分促成血小板与其周围环境的通讯尚不清楚,还需要开展进一步研究。



推荐阅读原文:
Platelet biology and functions: new concepts and clinical perspectives.

Platelets - blood cells continuously produced from megakaryocytes mainly in the bone marrow - are implicated not only in haemostasis and arterial thrombosis, but also in other physiological and pathophysiological processes. This Review describes current evidence for the heterogeneity in platelet structure, age, and activation properties, with consequences for a diversity of platelet functions. Signalling processes of platelet populations involved in thrombus formation with ongoing coagulation are well understood. Genetic approaches have provided information on multiple genes related to normal haemostasis, such as those encoding receptors and signalling or secretory proteins, that determine platelet count and/or responsiveness. As highly responsive and secretory cells, platelets can alter the environment through the release of growth factors, chemokines, coagulant factors, RNA species, and extracellular vesicles. Conversely, platelets will also adapt to their environment. In disease states, platelets can be positively primed to reach a pre-activated condition. At the inflamed vessel wall, platelets interact with leukocytes and the coagulation system, interactions mediating thromboinflammation. With current antiplatelet therapies invariably causing bleeding as an undesired adverse effect, novel therapies can be more beneficial if directed against specific platelet responses, populations, interactions, or priming conditions. On the basis of these novel concepts and processes, we discuss several initiatives to target platelets therapeutically.






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