LYMPHOCYTE/ERYTHROCYTE ADHESION IN SICKLE CELL DISEASE

镰状细胞病中的淋巴细胞/红细胞粘附

• 批准号: 6325888
• 负责人: DAVID E GOLAN
• 金额: $ 26.66万
• 依托单位: BOSTON MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6325888
• 关键词: CD2 molecule; T lymphocyte; cell adhesion; cytokine; electron microscopy; erythrocyte membrane; genetically modified animals; hemoglobin Ss; human subject; intravital microscopy; laboratory mouse; lasers; leukocyte activation /transformation; leukocyte adhesion molecules; membrane lipids; membrane reconstitution /synthesis; phospholipids; protein binding; sickle cell anemia; sickle cell crisis; time resolved data; tissue /cell culture; vascular endothelium; vascular resistance; video microscopy

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

细胞膜是细胞外信号传递的主要媒介 被传递到细胞内部。然而，在其他情况下， 细胞内事件可以影响细胞与其 细胞外环境镰状细胞瘤的主要病理生理事件 镰状红细胞内血红蛋白S的聚合 （红细胞），导致镰状红细胞膜的改变， 镰状红细胞和其他血细胞之间的相互作用， 内皮细胞和单核细胞/巨噬细胞。在调查 介导这些相互作用的分子机制， 发现了一个新的现象， 在血液中发现了涉及镰状红细胞和T淋巴细胞的结合物 纯合子型镰状细胞病（SS）患者。这些缀合物 可能参与导致溶血的病理生理过程 和血管闭塞危象，镰状细胞病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， 视频显微镜技术来研究分子机制， 介导镰状红细胞与T淋巴细胞的粘附，包括 淋巴细胞表面上的CD 2和CD 58（LFA-1）之间的结合相互作用 3)以及镰状红细胞膜 T淋巴细胞膜改变，以增强淋巴细胞-RBC结合 形成