Wun T, Paglieroni T, Field C L, Welborn J, Cheung A, Walker N J, Tablin F
Division of Hematology-Oncology, UC Davis, School of Medicine, Sacramento 95817, USA.
J Investig Med. 1999 Mar;47(3):121-7.
The abnormal adherence of sickle red blood cells (sRBC) to other cell types likely contributes to vaso-occlusion. Increased numbers of platelet-erythrocyte aggregates (PEA) and platelet activation have been described in sickle cell disease. The present study was undertaken to determine the contribution, if any, of the extracellular matrix protein thrombospondin to the adhesion of sRBC and platelets.
Platelet activation and PEA were measured using fluorescent-labeled monoclonal antibodies and flow cytometry. Platelet red-cell adhesion was measured by a gravity sedimentation assay. Erythrocyte-bound thrombospondin (TSP) was determined by enzyme-linked immunoabsorbant assay (ELISA).
Our studies demonstrate significant platelet activation and adhesion of sRBC to platelets in sickle cell disease. Thrombospondin was detected on sRBC. There was variable inhibition of sRBC-platelet adhesion by antibodies to CD36 (thrombospondin receptor) and antibodies to thrombospondin.
Thrombospondin on sRBC may mediate, at least in part, sRBC-platelet adhesion in sickle cell disease. The study of heterotypic cell-cell interactions is important in understanding the pathogenesis of vaso-occlusion in sickle cell disease.
镰状红细胞（sRBC）与其他细胞类型的异常黏附可能导致血管阻塞。镰状细胞病患者体内血小板-红细胞聚集体（PEA）数量增加且血小板活化增强。本研究旨在确定细胞外基质蛋白血小板反应蛋白对sRBC与血小板黏附的作用（若有）。
使用荧光标记的单克隆抗体和流式细胞术检测血小板活化及PEA。通过重力沉降试验检测血小板与红细胞的黏附。采用酶联免疫吸附测定法（ELISA）测定红细胞结合的血小板反应蛋白（TSP）。
我们的研究表明，镰状细胞病患者存在显著的血小板活化以及sRBC与血小板的黏附。在sRBC上检测到了血小板反应蛋白。抗CD36（血小板反应蛋白受体）抗体和抗血小板反应蛋白抗体对sRBC-血小板黏附有不同程度的抑制作用。
sRBC上的血小板反应蛋白可能至少部分介导了镰状细胞病中sRBC与血小板的黏附。异型细胞间相互作用的研究对于理解镰状细胞病血管阻塞的发病机制具有重要意义。
