A novel pathway of rapid TLR-triggered activation of integrin-dependent leukocyte adhesion that requires Rap1 GTPase.
Mol Biol Cell
; 25(19): 2948-55, 2014 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-25057020
ABSTRACT
Rapid ß2-integrin activation is indispensable for leukocyte adhesion and recruitment to sites of infection and is mediated by chemokine- or P-selectin glycoprotein ligand-1-induced inside-out signaling. Here we uncovered a novel pathway for rapid activation of integrin-dependent leukocyte adhesion, triggered by toll-like receptor (TLR)-mediated signaling. TLR2 or TLR5 ligation rapidly activated integrin-dependent leukocyte adhesion to immobilized ICAM-1 and fibronectin. Consistently, in vivo administration of the TLR2-ligand Pam3CSK4 increased integrin-dependent slow rolling and adhesion to endothelium within minutes, as identified by intravital microscopy in the cremaster model. TLR2 and TLR5 ligation increased ß2-integrin affinity, as assessed by the detection of activation-dependent neoepitopes. TLR2- and TLR5-triggered integrin activation in leukocytes required enhanced Rap1 GTPase activity, which was mediated by Rac1 activation and NADPH oxidase-2-dependent reactive oxygen species production. This novel direct pathway linking initial pathogen recognition by TLRs to rapid ß2-integrin activation may critically regulate acute leukocyte infiltration to sites of pathogen invasion.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Adesão Celular
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Proteínas rap1 de Ligação ao GTP
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Receptor 2 Toll-Like
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Receptor 5 Toll-Like
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Leucócitos
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article