Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity.
J Cell Sci
; 124(Pt 9): 1477-85, 2011 May 01.
Article
em En
| MEDLINE
| ID: mdl-21486942
ABSTRACT
PECAM-1 (CD31) is a cellular adhesion and signaling receptor that is highly expressed at endothelial cell-cell junctions in confluent vascular beds. Previous studies have implicated PECAM-1 in the maintenance of vascular barrier integrity; however, the mechanisms behind PECAM-1-mediated barrier protection are still poorly understood. The goal of the present study, therefore, was to examine the pertinent biological properties of PECAM-1 (i.e. adhesion and/or signaling) that allow it to support barrier integrity. We found that, compared with PECAM-1-deficient endothelial cells, PECAM-1-expressing endothelial cell monolayers exhibit increased steady-state barrier function, as well as more rapid restoration of barrier integrity following thrombin-induced perturbation of the endothelial cell monolayer. The majority of PECAM-1-mediated barrier protection was found to be due to the ability of PECAM-1 to interact homophilically and become localized to cell-cell junctions, because a homophilic binding-crippled mutant form of PECAM-1 was unable to support efficient barrier function when re-expressed in cells. By contrast, cells expressing PECAM-1 variants lacking residues known to be involved in PECAM-1-mediated signal transduction exhibited normal to near-normal barrier integrity. Taken together, these studies suggest that PECAM-1-PECAM-1 homophilic interactions are more important than its signaling function for maintaining the integrity of endothelial cell junctions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Molécula-1 de Adesão Celular Endotelial a Plaquetas
/
Células Endoteliais
/
Junções Intercelulares
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article