Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction
Activation of sickle red blood cell adhesion via integrin-associated protein/CD47-induced signal transduction
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DOI：
10.1172/jci10817
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发表时间：
2001-06-01
影响因子：
15.9
通讯作者：
Parise, LV
中科院分区：
文献类型：
--
作者：
Brittain, JE;Mlinar, KJ;Parise, LV
通常不知道外周人红细胞（RBC）响应于细胞信号传导而变得活化和粘附。然而，我们发现，可溶性血小板反应蛋白通过整合素相关蛋白（IAP; CD 47）通过激活SS RBC中的信号转导增加了镰状红细胞（SS RBC）的粘附性。这种受刺激的粘附需要IAP和剪切应力的占据，并且由大G蛋白和酪氨酸激酶的活化介导。来源于镰状细胞病（SCD）患者的富含网织红细胞的RBC对IAP诱导的活化反应最大。因此，这些研究建立外周SS红细胞作为信号细胞，响应IAP诱导的信号转导和剪切应力之间的新的协同作用，这表明新的治疗靶点SCD。
Peripheral human red blood cells (RBCs) are not generally known to become activated and adhesive in response to cell signaling. We show, however, that soluble thrombospondin via integrin-associated protein (IAP; CD47) increases the adhesiveness of sickle RBCs (SS RBCs) by activating signal transduction in the SS RBC. This stimulated adhesion requires occupancy of IAP and shear stress and is mediated by the activation of large G proteins and tyrosine kinases. Reticulocyte-enriched RBCs derived from sickle-cell disease (SCD) patients are most responsive to IAP-induced activation. These studies therefore establish peripheral SS RBCs as signaling cells that respond to a novel synergy between IAP-induced signal transduction and shear stress, suggesting new therapeutic targets in SCD.