title: Regulation of endothelial cell barrier function by antibody-driven affinity modulation of platelet endothelial cell adhesion molecule-1 (PECAM-1).
abstract: PECAM-1 is a 130-kDa member of the immunoglobulin (Ig) superfamily that is expressed on the surface of platelets and leukocytes, and at the intracellular junctions of confluent endothelial cell monolayers. Previous studies have shown that PECAM-1/PECAM-1 homophilic interactions play a key role in leukocyte transendothelial migration, in allowing PECAM-1 to serve as a mechanosensory complex in endothelial cells, in its ability to confer cytoprotection to proapoptotic stimuli, and in maintaining endothelial cell junctional integrity. To examine the adhesive properties of full-length PECAM-1 in a native lipid environment, we purified it from platelets and assembled it into phospholipid nanodiscs. PECAM-1-containing nanodiscs retained not only their ability to bind homophilically to PECAM-1-expressing cells, but exhibited regulatable adhesive interactions that could be modulated by ligands that bind membrane- proximal Ig Domain 6. This property was exploited to enhance the rate of barrier restoration in endothelial cell monolayers subjected to inflammatory challenge. The finding that the adhesive properties of PECAM-1 are regulatable suggests novel approaches for controlling endothelial cell migration and barrier function in a variety of vascular permeability disorders.
authors.forename: Heng
authors.initials: H
authors.lastname: Mei
authors.forename: Jay M
authors.initials: JM
authors.lastname: Campbell
authors.forename: Cathy M
authors.initials: CM
authors.lastname: Paddock
authors.forename: Panida
authors.initials: P
authors.lastname: Lertkiatmongkol
authors.forename: Michael W
authors.initials: MW
authors.lastname: Mosesson
authors.forename: Ralph
authors.initials: R
authors.lastname: Albrecht
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Newman
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008567:Membranes, Artificial; D010743:Phospholipids / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D014652:Vascular Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000906:Antibodies; D008567:Membranes, Artificial; D010743:Phospholipids; D019408:Platelet Endothelial Cell Adhesion Molecule-1