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Nat Immunol ; 13(1): 67-76, 2011 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-22138716

RESUMO

Chemokines presented by the endothelium are critical for integrin-dependent adhesion and transendothelial migration of naive and memory lymphocytes. Here we found that effector lymphocytes of the type 1 helper T cell (T(H)1 cell) and type 1 cytotoxic T cell (T(C)1 cell) subtypes expressed adhesive integrins that bypassed chemokine signals and established firm arrests on variably inflamed endothelial barriers. Nevertheless, the transendothelial migration of these lymphocytes strictly depended on signals from guanine nucleotide-binding proteins of the G(i) type and was promoted by multiple endothelium-derived inflammatory chemokines, even without outer endothelial surface exposure. Instead, transendothelial migration-promoting endothelial chemokines were stored in vesicles docked on actin fibers beneath the plasma membranes and were locally released within tight lymphocyte-endothelial synapses. Thus, effector T lymphocytes can cross inflamed barriers through contact-guided consumption of intraendothelial chemokines without surface-deposited chemokines or extraendothelial chemokine gradients.


Assuntos
Quimiocinas/metabolismo , Células Endoteliais/metabolismo , Linfócitos/imunologia , Migração Transendotelial e Transepitelial/imunologia , Vesículas Transportadoras/metabolismo , Animais , Membrana Celular/metabolismo , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Integrinas/metabolismo , Linfócitos/metabolismo , Linfócitos/ultraestrutura , Camundongos , Receptores CCR2/metabolismo , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/ultraestrutura , Fator de Necrose Tumoral alfa/farmacologia , Vasculite/imunologia , Vasculite/metabolismo
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