Chronic Immune Platelet Activation Is Followed by Platelet Refractoriness and Impaired Contractility.
Chronic Immune Platelet Activation Is Followed by Platelet Refractoriness and Impaired Contractility.
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慢性免疫性血小板活化后血小板不应性和收缩力受损。
DOI：
10.3390/ijms23137336
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发表时间：
2022-06-30
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
自身免疫性疾病，包括系统性红斑狼疮（SLE），具有与血小板功能改变相关的血栓形成和出血并发症的高风险。我们研究了SLE患者的血小板及其反应性。用流式细胞术检测血小板刺激前后磷脂酰丝氨酸、P-选择素和活性整合素αIIbβ3的表达。测量血浆中可溶性P-选择素。血小板驱动的凝块收缩的动力学进行了研究，以及扫描和透射电子显微镜未刺激的血小板。膜相关磷脂酰丝氨酸和血小板附着和可溶性P-选择素水平升高与IgG、抗dsDNA抗体和循环免疫复合物的滴度直接相关。形态学上，SLE患者的血小板失去了其静止的盘状形状，形成膜突起和聚集体，并且具有粗糙的质膜。血小板活化的迹象与对生理刺激的反应性降低和收缩力受损（显示血小板衰竭和不应性）矛盾相关。血小板活化具有多种促凝血作用，并且不能完全收缩（收缩）血凝块可以是与改变的凝块渗透性、凝块对纤维蛋白溶解的敏感性、阻塞性和栓塞性相关的出血或促血栓形成机制。因此，继发性血小板功能障碍的慢性免疫血小板活化构成了支持自身免疫性疾病（如SLE）中止血障碍的未充分研究的致病机制。
Autoimmune diseases, including systemic lupus erythematosus (SLE), have a high risk of thrombotic and hemorrhagic complications associated with altered platelet functionality. We studied platelets from the blood of SLE patients and their reactivity. The surface expression of phosphatidylserine, P-selectin, and active integrin αIIbβ3 were measured using flow cytometry before and after platelet stimulation. Soluble P-selectin was measured in plasma. The kinetics of platelet-driven clot contraction was studied, as well as scanning and transmission electron microscopy of unstimulated platelets. Elevated levels of membrane-associated phosphatidylserine and platelet-attached and soluble P-selectin correlated directly with the titers of IgG, anti-dsDNA-antibodies, and circulating immune complexes. Morphologically, platelets in SLE lost their resting discoid shape, formed membrane protrusions and aggregates, and had a rough plasma membrane. The signs of platelet activation were associated paradoxically with reduced reactivity to a physiological stimulus and impaired contractility that revealed platelet exhaustion and refractoriness. Platelet activation has multiple pro-coagulant effects, and the inability to fully contract (retract) blood clots can be either a hemorrhagic or pro-thrombotic mechanism related to altered clot permeability, sensitivity of clots to fibrinolysis, obstructiveness, and embologenicity. Therefore, chronic immune platelet activation followed by secondary platelet dysfunction comprise an understudied pathogenic mechanism that supports hemostatic disorders in autoimmune diseases, such as SLE.
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