Unknown

Dataset Information

0

Receptor for advanced glycation end products (RAGE) on iNKT cells mediates lung ischemia-reperfusion injury.


ABSTRACT: Activation of invariant natural killer T (iNKT) cells and signaling through receptor for advanced glycation end products (RAGE) are known to independently mediate lung ischemia-reperfusion (IR) injury. This study tests the hypothesis that activation of RAGE specifically on iNKT cells via alveolar macrophage-produced high mobility group box 1 (HMGB1) is critical for the initiation of lung IR injury. A murine in vivo hilar clamp model was utilized, which demonstrated that RAGE(-/-) mice were significantly protected from IR injury. Treatment of WT mice with soluble RAGE (a decoy receptor), or anti-HMGB1 antibody, attenuated lung IR injury and inflammation, whereas treatment with recombinant HMGB1 enhanced IR injury in WT mice but not RAGE(-/-) mice. Importantly, lung dysfunction, cytokine production and neutrophil infiltration were significantly attenuated after IR in J?18(-/-) mice reconstituted with RAGE(-/-) iNKT cells (versus WT iNKT cells). In vitro studies demonstrated that, after hypoxia-reoxygenation, alveolar macrophage-derived HMGB1 augmented IL-17 production from iNKT cells in a RAGE-dependent manner. These results suggest that HMGB1-mediated RAGE activation on iNKT cells is critical for initiation of lung IR injury and that a crosstalk between macrophages and iNKT cells via the HMGB1/RAGE axis mediates IL-17 production by iNKT cells causing neutrophil infiltration and lung IR injury.

SUBMITTER: Sharma AK 

PROVIDER: S-EPMC3776006 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4057161 | BioStudies
2012-01-01 | S-EPMC3326427 | BioStudies
2020-01-01 | S-EPMC7025070 | BioStudies
2014-01-01 | S-EPMC5450936 | BioStudies
1000-01-01 | S-EPMC3137143 | BioStudies
2016-01-01 | S-EPMC5133955 | BioStudies
2018-01-01 | S-EPMC6240507 | BioStudies
2019-01-01 | S-EPMC6338799 | BioStudies
2013-01-01 | S-EPMC3859028 | BioStudies
2017-01-01 | S-EPMC5543147 | BioStudies