Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation

Author:

Barreiro Olga1,Yáñez-Mó María1,Sala-Valdés Mónica1,Gutiérrez-López María Dolores1,Ovalle Susana1,Higginbottom Adrian1,Monk Peter N.1,Cabañas Carlos1,Sánchez-Madrid Francisco1

Affiliation:

1. From the Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain; Instituto de Farmacología y Toxicología, Consejo Superior de Investigaciones Científicas–Universidad Complutense de Madrid (CSIC-UCM), Facultad de Medicina, Universidad Complutense, Madrid, Spain; and Department of Academic Neurology, The Medical School, University of Sheffield, United Kingdom.

Abstract

AbstractTetraspanins associate with several transmembrane proteins forming microdomains involved in intercellular adhesion and migration. Here, we show that endothelial tetraspanins relocalize to the contact site with transmigrating leukocytes and associate laterally with both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Alteration of endothelial tetraspanin microdomains by CD9–large extracellular loop (LEL)–glutathione S–transferase (GST) peptides or CD9/CD151 siRNA oligonucleotides interfered with ICAM-1 and VCAM-1 function, preventing lymphocyte transendothelial migration and increasing lymphocyte detachment under shear flow. Heterotypic intercellular adhesion mediated by VCAM-1 or ICAM-1 was augmented when expressed exogenously in the appropriate tetraspanin environment. Therefore, tetraspanin microdomains have a crucial role in the proper adhesive function of ICAM-1 and VCAM-1 during leukocyte adhesion and transendothelial migration.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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