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

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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.