Biochemical isolation and characterization of the lateral border recycling compartment from human endothelial cells and determination of its regulatory role for transendothelial migration of leukocytes

人内皮细胞侧缘回收区室的生化分离和表征及其对白细胞跨内皮迁移的调节作用的测定

• 批准号: 20374704
• 负责人: Dr. Claas Rüffer
• 金额: --
• 依托单位: Feinberg School of Medicine
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/20374704?language=en
• 关键词: Biochemical; isolation; characterization; lateral; border

Platelet-endothelial-cell adhesion molecule 1 (PECAM-1) belongs to the immunoglobulin (Ig) superfamily of cell adhesion molecules. The expression of PECAM-1 is restricted to cells of the vascular system. In confluent endothelial cells PECAM-1 localizes to cell-cell borders and to the lumen-facing plasmamembrane of the endothelium in blood vessels. PECAM-1 plays an important role in the transmigration of neutrophils, monocytes and natural killer cells, both in vivo and in vitro. Blocking PECAM-1 with anti-PECAM-1 antibodies or soluble PECAM-1-Fc chimera selectively inhibits transendothelial migration by 70-90%. In resting endothelial cells, PECAM-1 cycles between the cell surface and a novel internal PECAM-1-bearing compartment. PECAM-1 constitutively recycles from this compartment to the endothelial cell border. During diapedesis the recycling PECAM is directly targeted to the zone of the endothelial cell border that contacts the transmigrating monocytes, rather then recycling evently along the lateral cell borders.The major goal of this project is to perform a thorough biochemical analysis of this lateral compartment. This should give further insights into the role of this compartment in the process of transendothelial migration.

血小板内皮细胞粘附分子1（PECAM-1）属于免疫球蛋白（IG）超家族的细胞粘附分子。PECAM-1的表达仅限于血管系统的细胞。在汇合的内皮细胞中，PECAM-1定位于细胞-细胞边界和血管内皮的面向管腔的质膜。PECAM-1在体内和体外中性粒细胞、单核细胞和自然杀伤细胞的迁移中起重要作用。用抗PECAM-1抗体或可溶性PECAM-1-Fc嵌合体阻断PECAM-1可选择性抑制70- 90%的跨内皮迁移。在静息内皮细胞中，PECAM-1在细胞表面和新的内部PECAM-1承载区室之间循环。PECAM-1组成性地从该隔室向内皮细胞边界延伸。在渗出过程中，PECAM的再循环直接作用于与迁移的单核细胞接触的内皮细胞边缘区，而不是沿着细胞的侧边缘再循环。这将进一步深入了解这一车厢的跨内皮迁移的过程中的作用。