Wick T M, Moake J L, Udden M M, McIntire L V
Cox Laboratory for Biomedical Engineering, Rice University, Houston, Texas 77251-1892.
Am J Hematol. 1993 Mar;42(3):284-92. doi: 10.1002/ajh.2830420308.
Sickle red blood cells (RBC) suspended with endothelial cell (EC)-derived unusually large (UL) von Willebrand factor (vWF) multimers, but not large plasma vWF forms, adhered to human venous EC under shear flow conditions. When sickle RBC were separated by density gradient centrifugation, fractions rich in less dense RBC were the most adhesive to EC in the presence of ULvWF. Incubation of sickle RBC with monoclonal antibodies against platelet surface receptors GPIb or GPIIb/IIIa, or with the integrin receptor agonist Arg-Gly-Asp-Ser (RGDS) decreased the ULvWF-mediated sickle RBC adhesion to EC 84%, > 99%, and 90%, respectively. When incubated with EC before the flow studies, anti-GPIb antibody and RGDS inhibited the ULvWF-mediated sickle RBC adhesion to EC. ULvWF also promoted the adhesion to EC of nonsickle RBC (HbAA) from patients with an increased proportion of young erythrocytes. When the EC supernatant was depleted of most vWF forms, young nonsickle RBC adhesion decreased by 90%. Preincubation of young nonsickle RBC with anti-GPIb antibody, anti-GPIIb/IIIa antibody, or RGDS inhibited the ULvWF-mediated young RBC adhesion to EC by 47%, 88%, and 92%, respectively. These data indicate that (1) low-density erythrocyte fractions enriched in young sickle or young nonsickle RBC are capable of binding ULvWF multimers via GPIb-like and GPIIb/IIIa-like receptors; (2) the RBC vWF receptors are lost or modified as erythrocytes age in the circulation; and (3) ULvWF/RBC complexes also bind to EC via a GPIb-like receptor.
镰状红细胞（RBC）与内皮细胞（EC）衍生的异常大（UL）的血管性血友病因子（vWF）多聚体而非血浆中的大vWF形式一起悬浮时，在剪切流条件下会黏附于人类静脉EC。当通过密度梯度离心分离镰状RBC时，富含低密度RBC的组分在存在ULvWF的情况下对EC的黏附性最强。用抗血小板表面受体GPIb或GPIIb/IIIa的单克隆抗体或整合素受体激动剂Arg-Gly-Asp-Ser（RGDS）孵育镰状RBC，可分别使ULvWF介导的镰状RBC对EC的黏附降低84%、>99%和90%。在流动研究前与EC一起孵育时，抗GPIb抗体和RGDS可抑制ULvWF介导的镰状RBC对EC的黏附。ULvWF还促进了年轻红细胞比例增加的患者的非镰状RBC（HbAA）对EC的黏附。当EC上清液中大部分vWF形式被去除时，年轻非镰状RBC的黏附降低了90%。用抗GPIb抗体、抗GPIIb/IIIa抗体或RGDS预孵育年轻非镰状RBC，可分别使ULvWF介导的年轻RBC对EC的黏附降低47%、88%和92%。这些数据表明：（1）富含年轻镰状或年轻非镰状RBC的低密度红细胞组分能够通过类GPIb和类GPIIb/IIIa受体结合ULvWF多聚体；（2）随着红细胞在循环中老化，RBC的vWF受体丢失或发生改变；（3）ULvWF/RBC复合物也通过类GPIb受体与EC结合。
