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Nat Commun ; 8(1): 1010, 2017 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-29044117

RESUMO

Effector T cell migration through tissues can enable control of infection or mediate inflammatory damage. Nevertheless, the molecular mechanisms that regulate migration of effector T cells within the interstitial space of inflamed lungs are incompletely understood. Here, we show T cell migration in a mouse model of acute lung injury with two-photon imaging of intact lung tissue. Computational analysis indicates that T cells migrate with an intermittent mode, switching between confined and almost straight migration, guided by lung-associated vasculature. Rho-associated protein kinase (ROCK) is required for both high-speed migration and straight motion. By contrast, inhibition of Gαi signaling with pertussis toxin affects speed but not the intermittent migration of lung-infiltrating T cells. Computational modeling shows that an intermittent migration pattern balances both search area and the duration of contacts between T cells and target cells. These data identify that ROCK-dependent intermittent T cell migration regulates tissue-sampling during acute lung injury.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Movimento Celular , Linfócitos T/metabolismo , Quinases Associadas a rho/metabolismo , Lesão Pulmonar Aguda/patologia , Algoritmos , Animais , Rastreamento de Células/métodos , Feminino , Pulmão/diagnóstico por imagem , Pulmão/metabolismo , Pulmão/patologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica
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