Sickle cell adhesion to laminin:: Potential role for the α5 chain
Sickle cell adhesion to laminin:: Potential role for the α5 chain
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DOI：
10.1182/blood.v92.8.2951.420k30_2951_2958
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发表时间：
1998-10-15
期刊：
影响因子：
20.3
通讯作者：
Parise, LV
中科院分区：
文献类型：
--
作者：
Lee, SP;Cunningham, ML;Parise, LV
镰状红细胞（RBC）与内皮和暴露的内皮下蛋白的粘附被认为导致镰状细胞病中的血管闭塞。层粘连蛋白是内皮下层的主要成分，支持镰状红细胞的显着粘附，但不支持正常红细胞。本研究的目的是使用旨在模拟通过毛细血管后微静脉的生理流动的流动粘附测定来定义人层粘连蛋白制剂中镰状红细胞的粘附区域。由于镰状红细胞不粘附常见的层粘连蛋白污染物巢蛋白或 IV 型胶原蛋白，因此这些蛋白质都不可能对观察到的层粘连蛋白粘附有贡献。已知的层粘连蛋白粘附区域既不支持也不抑制镰状红细胞对层粘连蛋白的粘附，这表明了先前在其他层粘连蛋白粘附研究中未表征的粘附机制。此外，镰状红细胞不粘附小鼠 EHS 层粘连蛋白或人层粘连蛋白-2（merosin），从而消除了作为镰状细胞粘附介质的 α1、α2、β1 和 γ1 链。单克隆抗体 4C7 与层粘连蛋白 α 5 链的 G 结构域或其附近结合，显着抑制镰状红细胞粘附。这些结果表明，镰状红细胞的粘附区域包含在层粘连蛋白 α 5 链内。 (C) 1998 年，美国血液学会。
sickle red blood cell (RBC) adhesion to the endothelium and to exposed, underlying subendothelial proteins is believed to contribute to vascular occlusion in sickle cell disease. Laminin, a major component of the subendothelium, supports significant adhesion of sickle, but not normal RBCs, The purpose of this study was to define the adhesive region for sickle RBCs within a human laminin preparation using a flow adhesion assay designed to mimic physiologic flow through postcapillary venules. Because sickle RBCs did not adhere to the common laminin contaminants entactin or collagen type IV, neither of these proteins are likely to contribute to the observed adhesion to laminin. Known adhesive regions of laminin neither supported nor inhibited sickle RBC adhesion to laminin, suggesting a mechanism of adhesion previously uncharacterized in other laminin adhesion studies. Moreover, sickle RBCs did not adhere to mouse EHS laminin or to human laminin-2 (merosin), eliminating the alpha 1, alpha 2, beta 1, and gamma 1 chains as mediators of sickle cell adhesion. The monoclonal antibody 4C7, which binds at or near the G-domain of the laminin alpha 5 chain, significantly inhibited sickle RBC adhesion. These results suggest that an adhesive region for sickle RBCs is contained within the laminin alpha 5 chain. (C) 1998 by The American Society of Hematology.