NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome
Autor: | Laura C. Whitmore, Elizabeth A. Newell, Jessica G. Moreland, Brieanna M. Hilkin, Jessica S. Hook, Kelli L. Goss |
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Rok vydání: | 2014 |
Předmět: |
Pulmonary and Respiratory Medicine
Male Pathology medicine.medical_specialty Physiology Multiple Organ Failure Inflammation Bone Marrow Cells Lung injury Systemic inflammation Proinflammatory cytokine Mice Physiology (medical) Intensive care Medicine Animals Lung Mice Knockout Membrane Glycoproteins business.industry Macrophages Zymosan NADPH Oxidases Cell Biology Lung Injury Articles Macrophage Activation medicine.disease Systemic Inflammatory Response Syndrome Systemic inflammatory response syndrome Mice Inbred C57BL Disease Models Animal medicine.anatomical_structure Neutrophil Infiltration Immunology NADPH Oxidase 2 cardiovascular system Cytokines medicine.symptom business Multiple organ dysfunction syndrome Bronchoalveolar Lavage Fluid circulatory and respiratory physiology |
Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 307(1) |
ISSN: | 1522-1504 |
Popis: | 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. |
Databáze: | OpenAIRE |
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