Faculty Collaboration Database

Regulation of endothelial cell barrier function by antibody-driven affinity modulation of platelet endothelial cell adhesion molecule-1 (PECAM-1). J Biol Chem 2014 Jul 25;289(30):20836-44

Date

06/18/2014

Pubmed ID

24936065

Pubmed Central ID

PMC4110291

DOI

10.1074/jbc.M114.557454

Scopus ID

2-s2.0-84905407842 (requires institutional sign-in at Scopus site)   26 Citations

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.

Author List

Mei H, Campbell JM, Paddock CM, Lertkiatmongkol P, Mosesson MW, Albrecht R, Newman PJ

Author

Peter J. Newman PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antibodies
Capillary Permeability
Cell Movement
HEK293 Cells
Human Umbilical Vein Endothelial Cells
Humans
Membranes, Artificial
Phospholipids
Platelet Endothelial Cell Adhesion Molecule-1
Protein Structure, Tertiary
Vascular Diseases