Intratracheal Injection of A_2AR Selective Agonist Mimics Protective Effects of Hypoxia

Abstract

<div><p>(A) IT injection of the A_2AR agonist CGS21680 into endotoxin-inflamed lungs provides protection similar to that observed in hypoxia-treated mice. Number of PMNs recovered after 48 h by BAL from endotoxin-injected animals that were kept at normal 21% oxygen atmosphere was significantly diminished by IT injections of CGS21680 compared to placebo-treated mice. Lung PMNs (left graph) from A_2AR agonist-treated animals also produced lower levels of reactive oxygen metabolites (H₂O₂; right graph).</p> <p>(B) Significantly decreased lung vascular permeability (protein in BAL; left graph) and improved lung gas exchange (p_aO₂; right graph) in endotoxin-injected mice after treatment with the A_2AR agonist CGS21680.</p> <p>(C) Histologic evidence for the lung tissue-protecting effects of A_2AR agonist during endotoxin- and oxygenation-induced lung damage. Quantitative analysis of lung histopathology by a pathologist blinded to the experimental design revealed inhibition of PMN sequestration in IT LPS-injected mice after treatment with the A_2AR-selective agonist CGS21680 for 48 h. The lung tissue damage was also significantly decreased as assessed by the LIS (<i>n</i> = 9, mean ± standard deviation). Representative H&E-stained slices in the right two photomicrographs show less intracapillary PMN sequestration and almost no intraalveolar accumulation of PMNs in CGS21680-treated mice. These CGS21680-induced changes are similar to those observed for the effects of hypoxia on endotoxin- injected animals (compare with <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0030174#pbio-0030174-g006" target="_blank">Figure 6</a>C).</p></div