Ser/Thr protein kinase Bβ-NADPH oxidase 2 signaling in thromboinflammation.
Ser/Thr protein kinase Bβ-NADPH oxidase 2 signaling in thromboinflammation.
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DOI：
10.1097/moh.0000000000000365
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发表时间：
2017-09
影响因子：
3.2
通讯作者：
Cho J
中科院分区：
文献类型：
--
作者：
Li J;Cho J
中性粒细胞和血小板之间的相互作用有助于血栓炎性疾病的进展。然而，人们对这些相互作用的调控机制知之甚少。本文综述了丝氨酸/苏氨酸蛋白激酶B (AKT)2- nadph氧化酶2 （NOX2）信号在调节中性粒细胞和血小板活化及其在血栓炎症条件下的异型相互作用中的关键作用。越来越多的证据表明，在治疗炎症和血栓同时发生的血栓炎性疾病时，需要考虑血小板、白细胞和凝血。除了血浆蛋白和细胞内信号分子外，活化的白细胞产生的细胞外活性氧（ROS）可能是血栓炎性疾病病理生理中的一个重要因素。最近的研究表明，AKT2-NOX2信号在Ca2+动员、ROS生成、脱颗粒和细胞表面分子配体结合功能的控制中起关键作用，从而促进血栓炎症中的异型细胞-细胞相互作用。这些发现为预防和治疗血栓炎性疾病提供了新的有吸引力的治疗靶点。最近关于调节中性粒细胞-血小板相互作用的分子机制的发现弥补了我们对复杂的信号通路加剧血栓炎症条件的认识上的一些空白。
Interactions between neutrophils and platelets contribute to the progression of thromboinflammatory disease. However, the regulatory mechanism governing these interactions is poorly understood. The present review focuses on the crucial role of Ser/Thr protein kinase B (AKT)2-NADPH oxidase 2 (NOX2) signaling in regulating neutrophil and platelet activation and their heterotypic interactions under thromboinflammatory conditions. Growing evidence has shown that platelets, leukocytes, and blood coagulation need to be considered to treat thromboinflammatory disease in which inflammation and thrombosis occur concurrently. In addition to plasma proteins and intracellular signaling molecules, extracellular reactive oxygen species (ROS) produced from activated leukocytes could be an important factor in the pathophysiology of thromboinflammatory disease. Recent studies reveal that AKT2-NOX2 signaling has critical roles in Ca2+ mobilization, ROS generation, degranulation, and control of the ligand-binding function of cell surface molecules, thereby promoting heterotypic cell–cell interactions in thromboinflammation. These findings have provided novel insights into attractive therapeutic targets for the prevention and treatment of thromboinflammatory disease. Recent discoveries concerning molecular mechanisms regulating neutrophil–platelet interactions have bridged some gaps in our knowledge of the complicated signaling pathways exacerbating thromboinflammatory conditions.