dc.contributor.author | Mehl, Anne | en_US |
dc.contributor.author | Ghorbani, Peyman | en_US |
dc.contributor.author | Douda, David | en_US |
dc.contributor.author | Huang, Hailu | en_US |
dc.contributor.author | Palaniyar, Nades | en_US |
dc.contributor.author | Ratjen, Felix | en_US |
dc.contributor.author | Grasemann, Hartmut | en_US |
dc.date.accessioned | 2014-04-11T14:13:14Z | |
dc.date.issued | 2014 | en_US |
dc.identifier.citation | Mehl, Anne, Peyman Ghorbani, David Douda, Hailu Huang, Nades Palaniyar, Felix Ratjen, and Hartmut Grasemann. 2014. “Effect of Arginase Inhibition on Pulmonary L-Arginine Metabolism in Murine Pseudomonas Pneumonia.” PLoS ONE 9 (3): e90232. doi:10.1371/journal.pone.0090232. http://dx.doi.org/10.1371/journal.pone.0090232. | en |
dc.identifier.issn | 1932-6203 | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:12064553 | |
dc.description.abstract | Rationale: Infection of the lung with Pseudomonas aeruginosa results in upregulation of nitric oxide synthases (NOS) and arginase expression, and both enzymes compete for L-arginine as substrate. Nitric oxide (NO) production may be regulated by arginase as it controls L-arginine availability for NOS. We here studied the effect of systemic arginase inhibition on pulmonary L-arginine metabolism in Pseudomonas pneumonia in the mouse. Methods: Mice (C57BL/6, 8–10 weeks old, female) underwent direct tracheal instillation of Pseudomonas (PAO-1)-coated agar beads and were treated by repeated intra-peritoneal injections of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) or PBS until lungs were harvested on day 3 of the infection. L-arginine metabolites were quantified using liquid chromatography-tandem mass spectrometry, NO metabolites nitrate and nitrite by Griess reagent and cytokines by ELISA. Results: NO metabolite concentrations (48.5±2.9 vs. 10.9±2.3 µM, p<0.0001), as well as L-ornithine (29.6±1.7 vs 2.3±0.4 µM, p<0.0001), the product of arginase activity, were increased in Pseudomonas infected lungs compared to naïve controls. Concentrations of the NOS inhibitor asymmetric dimethylarginine (ADMA) were also increased (0.44±0.02 vs. 0.16±0.01 µM, p<0.0001). Arginase inhibition in the infected animals resulted in a significant decrease in L-ornithine (14.6±1.6 µM, p<0.0001) but increase in L-arginine concentration (p<0.001), L-arginine/ADMA ratio (p<0.001), L-arginine availability for NOS (p<0.001), and NO metabolite concentrations (67.3±5.7 µM, p<0.05). Arginase inhibitor treatment also resulted in an increase in NO metabolite levels in animals following intratracheal injection of LPS (p = 0.015). Arginase inhibition was not associated with an increase in inflammatory markers (IFN-γ, IL-1β, IL-6, MIP-2, KC or TNF-α) in lung. Concentrations of the L-ornithine-dependent polyamines putrescine, spermidine and spermine were increased in Pseudomonas infected lungs (p<0.001, respectively) but were unaffected by ABH treatment. Conclusions: Systemic arginase inhibition with ABH during Pseudomonas pneumonia in mice results in an increase in pulmonary NO formation but no pro-inflammatory effect. | en |
dc.language.iso | en_US | en |
dc.publisher | Public Library of Science | en |
dc.relation.isversionof | doi:10.1371/journal.pone.0090232 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940779/pdf/ | en |
dash.license | LAA | en_US |
dc.subject | Biology | en |
dc.subject | Biochemistry | en |
dc.subject | Neurochemistry | en |
dc.subject | Neurochemicals | en |
dc.subject | Nitric Oxide | en |
dc.subject | Neuroscience | en |
dc.subject | Medicine | en |
dc.subject | Anatomy and Physiology | en |
dc.subject | Respiratory System | en |
dc.subject | Infectious Diseases | en |
dc.subject | Bacterial Diseases | en |
dc.subject | Pseudomonas Infections | en |
dc.subject | Infectious Disease Modeling | en |
dc.subject | Pediatrics | en |
dc.subject | Pediatric Pulmonology | en |
dc.subject | Pulmonology | en |
dc.subject | Respiratory Infections | en |
dc.title | Effect of Arginase Inhibition on Pulmonary L-Arginine Metabolism in Murine Pseudomonas Pneumonia | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | PLoS ONE | en |
dash.depositing.author | Douda, David | en_US |
dc.date.available | 2014-04-11T14:13:14Z | |
dc.identifier.doi | 10.1371/journal.pone.0090232 | * |
dash.contributor.affiliated | Douda, David N. | |