Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation.
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.
Barreiro
Olga
O
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, C/Diego de León 62, 28006 Madrid, Spain.
Yáñez-Mó
María
M
Sala-Valdés
Mónica
M
Gutiérrez-López
María Dolores
MD
Ovalle
Susana
S
Higginbottom
Adrian
A
Monk
Peter N
PN
Cabañas
Carlos
C
Sánchez-Madrid
Francisco
F
D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021962:Membrane Microdomains / Q000276:immunology*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering; D060185:Tetraspanin 24; D060245:Tetraspanin 29; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015703:Antigens, CD; C554715:CD151 protein, human; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D060185:Tetraspanin 24; D060245:Tetraspanin 29; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1