1. Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation
- Author
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Francisco Sánchez-Madrid, Adrian Higginbottom, Mónica Sala-Valdés, Peter N. Monk, Olga Barreiro, María Dolores Gutiérrez-López, Susana Ovalle, María Yáñez-Mó, and Carlos Cabañas
- Subjects
Umbilical Veins ,Immunology ,Intercellular Adhesion Molecule-1 ,Vascular Cell Adhesion Molecule-1 ,Tetraspanin 24 ,Biology ,Biochemistry ,Tetraspanin 29 ,Membrane Microdomains ,Tetraspanin ,Antigens, CD ,Cell Movement ,Cell Adhesion ,Leukocytes ,Humans ,RNA, Small Interfering ,Cell adhesion ,Cells, Cultured ,Membrane Glycoproteins ,Cell adhesion molecule ,Cell migration ,Cell Biology ,Hematology ,Adhesion ,Transmembrane protein ,Protein Structure, Tertiary ,Cell biology ,Endothelial stem cell ,embryonic structures ,Endothelium, Vascular - Abstract
Tetraspanins 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.
- Published
- 2005
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