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

血小板内皮细胞粘附分子1 （PECAM-1）属于细胞粘附分子免疫球蛋白（Ig）超家族。PECAM-1的表达仅限于血管系统细胞。在合流内皮细胞中，PECAM-1定位于细胞-细胞边界和血管内皮面向管腔的质膜。PECAM-1在体内和体外均在中性粒细胞、单核细胞和自然杀伤细胞的转运中发挥重要作用。用抗PECAM-1抗体或可溶性PECAM-1- fc嵌合体阻断PECAM-1可选择性地抑制70-90%的跨内皮迁移。在静止的内皮细胞中，PECAM-1在细胞表面和一个新的内部携带PECAM-1的隔室之间循环。PECAM-1组成性地从这个隔室循环到内皮细胞边界。在渗出过程中，循环的PECAM直接靶向内皮细胞边界与迁移的单核细胞接触的区域，而不是沿外侧细胞边界循环。该项目的主要目标是对侧壁隔室进行彻底的生化分析。这将进一步深入了解该隔室在跨内皮细胞迁移过程中的作用。

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.