Document Detail


Inducible nitric oxide synthase contributes to immune dysfunction following trauma.
MedLine Citation:
PMID:  23042189     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Trauma results in a persistent depression in adaptive immunity, which contributes to patient morbidity and mortality. This state of immune paralysis following trauma is characterized by a change in cell-mediated immunity, specifically a depression in T-cell function and a shift toward TH2 T-cell phenotype. Upregulation of inducible nitric oxide synthase (iNOS) is well recognized after injury and contributes to the inflammatory response and organ damage early after trauma. However, it is unknown whether iNOS plays a role in adaptive immune dysfunction after trauma. This study utilized a murine model of severe peripheral tissue injury to show that iNOS is rapidly upregulated in macrophages and a (Gr-1-CD11b) myeloid-derived suppressor cell subpopulation in the spleen. Through the use of iNOS knockout mice, a specific iNOS inhibitor, and a nitric oxide (NO) scavenger, this study demonstrates that iNOS-derived NO is required for the depression in T-lymphocyte proliferation, interferon γ, and interleukin 2 production within the spleen at 48 h after trauma. These findings support the hypothesis that iNOS regulates immune suppression following trauma and suggest that targeting the sustained production of NO by iNOS may attenuate posttraumatic immune depression.
Authors:
Sophie S Darwiche; Roman Pfeifer; Christoph Menzel; Xiangcai Ruan; Marcus Hoffman; Changchun Cai; R Savanh Chanthaphavong; Patricia Loughran; Bruce R Pitt; Rosemary Hoffman; Hans-Christoph Pape; Timothy R Billiar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  38     ISSN:  1540-0514     ISO Abbreviation:  Shock     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-18     Completed Date:  2013-03-11     Revised Date:  2013-11-07    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  United States    
Other Details:
Languages:  eng     Pagination:  499-507     Citation Subset:  IM    
Affiliation:
Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Gene Expression Regulation, Enzymologic / genetics,  immunology
Immune Tolerance
Immunity, Cellular*
Interferon-gamma / genetics,  immunology,  metabolism
Interleukin-2 / genetics,  immunology,  metabolism
Macrophages / immunology*,  metabolism
Mice
Mice, Knockout
Nitric Oxide / biosynthesis,  genetics,  immunology
Nitric Oxide Synthase Type II / biosynthesis,  genetics,  immunology*
Spleen / immunology*,  metabolism
Th2 Cells / immunology*,  metabolism
Up-Regulation / genetics,  immunology
Wounds and Injuries / enzymology,  genetics,  immunology*
Grant Support
ID/Acronym/Agency:
R37 GM044100/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Interleukin-2; 10102-43-9/Nitric Oxide; 82115-62-6/Interferon-gamma; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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