Document Detail


Pulmonary natural killer T cells play an essential role in mediating hyperoxic acute lung injury.
MedLine Citation:
PMID:  23349052     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Critically ill patients are routinely exposed to high concentrations of supplemental oxygen for prolonged periods of time, which can be life-saving in the short term, but such exposure also causes severe lung injury and increases mortality. To address this therapeutic dilemma, we studied the mechanisms of the tissue-damaging effects of oxygen in mice. We show that pulmonary invariant natural killer T (iNKT) cells are unexpectedly crucial in the development of acute oxygen-induced lung injury. iNKT cells express high concentrations of the ectonucleotidase CD39, which regulates their state of activation. Both iNKT cell-deficient (Jα18(-/-)) and CD39-null mice tolerate hyperoxia, compared with wild-type control mice that exhibit severe lung injury. An adoptive transfer of wild-type iNKT cells into Jα18(-/-) mice results in hyperoxic lung injury, whereas the transfer of CD39-null iNKT cells does not. Pulmonary iNKT cell activation and proliferation are modulated by ATP-dependent purinergic signaling responses. Hyperoxic lung injury can be induced by selective P2X7-receptor blockade in CD39-null mice. Our data indicate that iNKT cells are involved in the pathogenesis of hyperoxic lung injury, and that tissue protection can be mediated through ATP-induced P2X7 receptor signaling, resulting in iNKT cell death. In conclusion, our data suggest that iNKT cells and purinergic signaling should be evaluated as potential novel therapeutic targets to prevent hyperoxic lung injury.
Authors:
Martina Nowak-Machen; Moritz Schmelzle; Dusan Hanidziar; Wolfgang Junger; Mark Exley; Leo Otterbein; Yan Wu; Eva Csizmadia; Glen Doherty; Michail Sitkovsky; Simon C Robson
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  48     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-02     Completed Date:  2013-06-25     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  601-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acute Lung Injury / etiology,  immunology*,  pathology
Adoptive Transfer
Animals
Antigens, CD / genetics,  metabolism
Apoptosis
Apyrase / genetics,  metabolism
Cell Proliferation
Cells, Cultured
Cytokines / secretion
Hyperoxia / complications,  immunology*,  pathology
Lung / immunology,  pathology
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Mice, Knockout
Natural Killer T-Cells / enzymology,  immunology*,  physiology
Neutrophil Infiltration
Neutrophils / immunology,  metabolism
Grant Support
ID/Acronym/Agency:
P01 AI045897/AI/NIAID NIH HHS; R01 GM097320/GM/NIGMS NIH HHS; R01 HL094400/HL/NHLBI NIH HHS; T32 GM007592-32/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Cytokines; EC 3.6.1.5/Apyrase; EC 3.6.1.5/CD39 antigen
Comments/Corrections

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