Lee S P, Cunningham M L, Hines P C, Joneckis C C, Orringer E P, Parise L V
Department of Biology, North Carolina Central University, Durham, NC, USA.
Blood. 1998 Oct 15;92(8):2951-8.
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 alpha1, alpha2, beta1, and gamma1 chains as mediators of sickle cell adhesion. The monoclonal antibody 4C7, which binds at or near the G-domain of the laminin alpha5 chain, significantly inhibited sickle RBC adhesion. These results suggest that an adhesive region for sickle RBCs is contained within the laminin alpha5 chain.
镰状红细胞（RBC）与内皮细胞以及暴露的内皮下蛋白的黏附被认为是导致镰状细胞病血管闭塞的原因。层粘连蛋白是内皮下的主要成分，它能支持镰状红细胞的显著黏附，但对正常红细胞则不然。本研究的目的是使用一种流动黏附试验来确定人层粘连蛋白制剂中镰状红细胞的黏附区域，该试验旨在模拟通过毛细血管后微静脉的生理流动。由于镰状红细胞不黏附于常见的层粘连蛋白污染物内动蛋白或IV型胶原蛋白，因此这两种蛋白质都不太可能导致观察到的对层粘连蛋白的黏附。层粘连蛋白已知的黏附区域既不支持也不抑制镰状红细胞对层粘连蛋白的黏附，这表明存在一种在其他层粘连蛋白黏附研究中尚未描述的黏附机制。此外，镰状红细胞不黏附于小鼠EHS层粘连蛋白或人层粘连蛋白-2（merosin），排除了α1、α2、β1和γ1链作为镰状细胞黏附的介质。在层粘连蛋白α5链的G结构域或其附近结合的单克隆抗体4C7显著抑制了镰状红细胞的黏附。这些结果表明，镰状红细胞的黏附区域包含在层粘连蛋白α5链内。
