Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8297610 | Biochemical and Biophysical Research Communications | 2013 | 5 Pages |
Abstract
S-nitrosoglutathione reductase (GSNOR) is a key denitrosylase and critically important for protecting immune and other cells from nitrosative stress. Pharmacological inhibition of GSNOR is being actively pursued as a therapeutic approach to increase S-nitrosoglutathione levels for the treatment of asthma and cystic fibrosis. In the present study, we employed GSNOR-deficient (GSNORâ/â) mice to investigate whether inactivation of GSNOR may increase susceptibility to pulmonary infection by Klebsiella pneumoniae, a common cause of nosocomial pneumonia. We found that compared to wild-type mice, bacterial colony forming units 48Â h after intranasal infection with K. pneumoniae were increased over 4-folds in lung and spleen and strikingly, over a 1000-folds in blood of GSNORâ/â mice. Lung injury was comparable between infected wild-type and GSNORâ/â mice, but inflammation and injury was significantly elevated in spleen of GSNORâ/â mice. Whereas all wild-type mice survived 48Â h after infection, 10 of 23 GSNORâ/â mice died. Thus, GSNOR appears to play a crucial role in controlling pulmonary and systemic infection by K. pneumoniae. Our results suggest that patients treated in clinical trials with inhibitors of GSNOR should be carefully monitored for signs of infection.
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Chi-Hui Tang, Eric J. Seeley, Xiaozhu Huang, Paul J. Wolters, Limin Liu,