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Protective effect of adenosine receptors against lipopolysaccharide-induced acute lung injury.
MedLine Citation:
PMID:  24414256     Owner:  NLM     Status:  Publisher    
Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) affect 200,000 people a year in the USA. Pulmonary vascular endothelial (EC) barrier compromise is a hallmark of these diseases. We have recently shown that extracellular adenosine enhances human pulmonary (EC) barrier via activation of adenosine receptors (ARs) in cell cultures. Based on these data, we hypothesized that activation of ARs might exert barrier protective effects in a model of ALI/ARDS in mice. To test this hypothesis we examined the effects of pre- and post-treatment of adenosine and 5'-N-Ethylcarboxamidoadenosine (NECA), a non-selective stable AR agonist, on LPS-induced lung injury. Mice were given vehicle or LPS followed by adenosine, NECA or vehicle instilled via the internal jugular vein (IJV). Post-experiment cell counts, Evans Blue Dye albumin (EBDA) extravasation, levels of proteins and inflammatory cytokines were analyzed. Harvested lungs were used for histology and myeloperoxidase (MPO) studies. Mice challenged with LPS alone demonstrated an inflammatory response typical of ALI. Cell counts, EBDA extravasation as well as levels of proteins and inflammatory cytokines were decreased in adenosine-treated mice. Histology displayed reduced infiltration of neutrophils. NECA had a similar effect on LPS-induced vascular barrier compromise. Importantly, treatment with adenosine or NECA restores lung vascular barrier and inflammation. Furthermore, adenosine significantly attenuated protein degradation of A2A and A3 receptors induced by LPS. Collectively, our results demonstrate that activation of adenosine receptors protects vascular barrier functions and reduced inflammation in LPS-induced ALI.
Joyce N Gonzales; Boris A Gorshkov; Matthew N Varn; Marina A Zemskova; Evgeny A Zemskov; Supriya Sridhar; Rudolf Lucas; Alexander D Verin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-1-10
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  -     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2014-1-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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