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NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome
Journal article   Open access   Peer reviewed

NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome

Laura C Whitmore, Kelli L Goss, Elizabeth A Newell, Brieanna M Hilkin, Jessica S Hook and Jessica G Moreland
American journal of physiology. Lung cellular and molecular physiology, Vol.307(1), pp.L71-L82
07/01/2014
DOI: 10.1152/ajplung.00054.2014
PMCID: PMC4080282
PMID: 24793165
url
https://doi.org/10.1152/ajplung.00054.2014View
Published (Version of record) Open Access

Abstract

Systemic inflammatory response syndrome (SIRS) is a common clinical condition in patients in intensive care units that can lead to complications, including multiple organ dysfunction syndrome (MODS). MODS carries a high mortality rate, and it is unclear why some patients resolve SIRS, whereas others develop MODS. Although oxidant stress has been implicated in the development of MODS, several recent studies have demonstrated a requirement for NADPH oxidase 2 (NOX2)-derived oxidants in limiting inflammation. We recently demonstrated that NOX2 protects against lung injury and mortality in a murine model of SIRS. In the present study, we investigated the role of NOX2-derived oxidants in the progression from SIRS to MODS. Using a murine model of sterile systemic inflammation, we observed significantly greater illness and subacute mortality in gp91(phox-/y) (NOX2-deficient) mice compared with wild-type mice. Cellular analysis revealed continued neutrophil recruitment to the peritoneum and lungs of the NOX2-deficient mice and altered activation states of both neutrophils and macrophages. Histological examination showed multiple organ pathology indicative of MODS in the NOX2-deficient mice, and several inflammatory cytokines were elevated in lungs of the NOX2-deficient mice. Overall, these data suggest that NOX2 function protects against the development of MODS and is required for normal resolution of systemic inflammation.
 Macrophage Activation - genetics Multiple Organ Failure - mortality Male Systemic Inflammatory Response Syndrome - genetics Lung Injury - mortality Bone Marrow Cells - immunology NADPH Oxidases - genetics Lung Injury - prevention & control Macrophages - immunology Cytokines - blood Cytokines - immunology Disease Models, Animal Neutrophil Infiltration - immunology Zymosan Lung - pathology Macrophage Activation - immunology Mice, Inbred C57BL Multiple Organ Failure - genetics NADPH Oxidase 2 Neutrophil Infiltration - genetics Membrane Glycoproteins - genetics Mice, Knockout Lung Injury - genetics Systemic Inflammatory Response Syndrome - pathology Animals Multiple Organ Failure - prevention & control Mice Bronchoalveolar Lavage Fluid - chemistry Systemic Inflammatory Response Syndrome - mortality

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