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, Jessica G. Moreland

Research output: Contribution to journalArticle

13 Scopus citations

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 gp91phox-/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.

Original languageEnglish (US)
Pages (from-to)L71-L82
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume307
Issue number1
DOIs
StatePublished - Jul 1 2014

    Fingerprint

Keywords

  • Chronic granulomatous disease
  • Inflammation
  • MODS
  • SIRS

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this