Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2852-2861 ◽  
Author(s):  
Olga Barreiro ◽  
María Yáñez-Mó ◽  
Mónica Sala-Valdés ◽  
María Dolores Gutiérrez-López ◽  
Susana Ovalle ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Transendothelial Migration ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Glutathione S Transferase ◽  
Large Extracellular Loop ◽  
And Migration ◽  
Cell Adhesion Molecule 1

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.

scholarly journals Rap1 translates chemokine signals to integrin activation, cell polarization, and motility across vascular endothelium under flow

2003 ◽  
Vol 161 (2) ◽  
pp. 417-427 ◽  
Author(s):  
Mika Shimonaka ◽  
Koko Katagiri ◽  
Toshinori Nakayama ◽  
Naoya Fujita ◽  
Takashi Tsuruo ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leading Edge ◽  
Intercellular Adhesion ◽  
Cell Polarization ◽  
Intercellular Adhesion Molecule ◽  
Integrin Activation ◽  
Intercellular Adhesion Molecule 1 ◽  
Circulating Lymphocytes ◽  
And Migration ◽  
Cell Adhesion Molecule 1

Chemokines arrest circulating lymphocytes within the vasculature through the rapid up-regulation of leukocyte integrin adhesive activity, promoting subsequent lymphocyte transmigration. However, the key regulatory molecules regulating this process have remained elusive. Here, we demonstrate that Rap1 plays a pivotal role in chemokine-induced integrin activation and migration. Rap1 was activated by secondary lymphoid tissue chemokine (SLC; CCL21) and stromal-derived factor 1 (CXCL4) treatment in lymphocytes within seconds. Inhibition of Rap1 by Spa1, a Rap1-specific GTPase-activating protein, abrogated chemokine-stimulated lymphocyte rapid adhesion to endothelial cells under flow via intercellular adhesion molecule 1. Expression of a dominant active Rap1V12 in lymphocytes stimulated shear-resistant adhesion, robust cell migration on immobilized intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, and transendothelial migration under flow. We also demonstrated that Rap1V12 expression in lymphocytes induced a polarized morphology, accompanied by the redistribution of CXCR4 and CD44 to the leading edge and uropod, respectively. Spa1 effectively suppressed this polarization after SLC treatment. This unique characteristic of Rap1 may control chemokine-induced lymphocyte extravasation.

scholarly journals Sialomucin CD 43 regulates T helper type 17 cell intercellular adhesion molecule 1 dependent adhesion, apical migration and transendothelial migration

Immunology ◽  
2019 ◽  
Vol 157 (1) ◽  
pp. 52-69 ◽  
Author(s):  
Francisco E. Velázquez ◽  
Marina Anastasiou ◽  
Francisco J. Carrillo‐Salinas ◽  
Njabulo Ngwenyama ◽  
Ane M. Salvador ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Transendothelial Migration ◽  
Intercellular Adhesion ◽  
Intercellular Adhesion Molecule ◽  
T Helper ◽  
Intercellular Adhesion Molecule 1 ◽  
Helper Type

Immune complexes alter cerebral microvessel permeability: roles of complement and leukocyte adhesion

2006 ◽  
Vol 291 (2) ◽  
pp. H694-H704 ◽  
Author(s):  
Karyn J. Lister ◽  
Michael J. Hickey
Keyword(s):  
Adhesion Molecule ◽  
Immune Complexes ◽  
Inflammatory Responses ◽  
Leukocyte Adhesion ◽  
Intercellular Adhesion ◽  
Microvascular Permeability ◽  
Intercellular Adhesion Molecule ◽  
Complement Pathway ◽  
Intercellular Adhesion Molecule 1 ◽  
Peripheral Tissues

Immune complexes (ICs) are potent inflammatory mediators in peripheral tissues. However, very few studies have examined the ability of ICs to induce inflammatory responses in the brain. Therefore, using preformed ICs or the reverse passive Arthus (RPA) model to localize ICs to the pial microvasculature of mice, we aimed to investigate the ability of ICs to induce an inflammatory response in the cerebral (pial) microvasculature. Application of preformed ICs immediately increased pial microvascular permeability, with a minimal change in leukocyte adhesion in pial postcapillary venules. In contrast, initiation of the RPA response in the pial microvasculature induced changes in cerebral microvascular permeability and increased leukocyte adhesion in pial postcapillary venules. The RPA response induced deposition of C3 in perivascular regions adjacent to sites of IC formation. Depletion of C3 abrogated RPA-induced microvascular permeability and leukocyte adhesion, indicating that the complement pathway was critical for this response. Inhibition of leukocyte adhesion via CD18 blockade also reduced IC-induced microvascular permeability. However, this did not require intercellular adhesion molecule-1, inasmuch as blockade of intercellular adhesion molecule-1 did not alter RPA-induced microvascular permeability and adhesion. These findings demonstrate that ICs are capable of rapidly inducing inflammatory responses in the cerebral microvasculature, with the complement pathway and leukocyte recruitment playing critical roles in microvascular dysfunction.

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