LYMPHOCYTE/ERYTHROCYTE ADHESION IN SICKLE CELL DISEASE

细胞膜主要是细胞外信号的传输器 被传输到细胞内部。然而，在其他情况下， 细胞内事件可以影响细胞与其相互作用 细胞外环境。镰刀病的主要病理生理事件 细胞性疾病，镰刀状红细胞内的血红蛋白聚合S (红细胞)，导致镰状红细胞膜的变化，从而增强 镰刀状红细胞与包括血管在内的其他血细胞的相互作用 内皮细胞和单核/巨噬细胞。在调查 调节这些相互作用的分子机制，我们的实验室有 做出了新的观察，大量的细胞-细胞 在血液中发现了含有镰状红细胞和T淋巴细胞的结合物 在纯合子(SS)镰状细胞病患者中。这些共轭化合物 可以参与导致溶血的病理生理序列 和血管闭塞危象，镰状细胞的两个主要临床问题 疾病。该项目的目标是使用时间分辨激光和 视频显微镜技术研究分子机制 介导镰状红细胞与T淋巴细胞的黏附，包括 淋巴细胞表面CD2与CD58(LFA-1)的结合作用 3)红细胞膜上的镰刀状红细胞膜的形成机制 改变T淋巴细胞膜以增强淋巴细胞与红细胞的结合 形成

Cell membranes are primarily transducers by which extracellular signals are transmitted to the interior of the cell. In other instances, however, intracellular events can effect the interactions of the cell with its extracellular environment. The primarily pathophysiologic event in sickle cell disease, polymerization of hemoglobin S within sickle red blood cells (RBCs), leads to alterations in sickle RBC membranes that enhance interactions between sickle RBCs and other blood cells, including vascular endothelial cells and monocytes/macrophages. In investigating the molecular mechanisms that mediate these interactions, our laboratory has made the novel observation that significant numbers of cell-cell conjugates involving sickle RBCs and T lymphocytes are found in the blood of patients with homozygous (SS) sickle cell disease. These conjugates could participate in the pathophysiologic sequences leading to hemolysis and vaso-occlusive crisis, the two major clinical problems in sickle cell disease. The objectives of this project are to use time-resolved laser and video microscopy techniques to investigate the molecular mechanisms that mediate adhesion of sickle RBCs to T lymphocytes, including the role of binding interactions between CD2 on the lymphocyte surface and CD58 (LFA- 3) on the RBC surface, and the mechanisms by which sickle RBC membranes and T lymphocyte membranes are altered to enhance lymphocyte-RBC conjugate formation