Back to Search
Start Over
A novel pathway of rapid TLR-triggered activation of integrin-dependent leukocyte adhesion that requires Rap1 GTPase
- Source :
- Molecular Biology of the Cell
- Publication Year :
- 2014
- Publisher :
- American Society for Cell Biology (ASCB), 2014.
-
Abstract
- TLR2 and TLR5 ligation directly induces β2-integrin activation, promoting cell adhesion to ICAM-1. Systemic in vivo administration of the TLR2 ligand Pam3CSK4 increases integrin-dependent adhesion to endothelium within minutes. The signaling pathway linking TLR ligation with β2-integin activation involves Rac-1, NADPH oxidase 2, and Rap1-GTPase.<br />Rapid β2-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 β2-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 β2-integrin activation may critically regulate acute leukocyte infiltration to sites of pathogen invasion.
- Subjects :
- rac1 GTP-Binding Protein
Chemokine
Integrin
Intercellular Adhesion Molecule-1
Biology
Lipopeptides
Cell Movement
Cell Adhesion
Leukocytes
Humans
NADH, NADPH Oxidoreductases
Endothelium
Cell Interactions
Cell adhesion
Molecular Biology
Cells, Cultured
Inflammation
Membrane Glycoproteins
NADPH Oxidases
rap1 GTP-Binding Proteins
Articles
Cell Biology
Toll-Like Receptor 2
Fibronectins
Cell biology
Enzyme Activation
Fibronectin
Toll-Like Receptor 5
TLR2
CD18 Antigens
NADPH Oxidase 2
biology.protein
Rap1
Reactive Oxygen Species
Intravital microscopy
Subjects
Details
- ISSN :
- 19394586 and 10591524
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....5861622dbd995c2ff098d864ad0c20be