Excessive Neutrophils and Neutrophil Extracellular Traps Contribute to Acute Lung Injury of Influenza Pneumonitis
By T. Narasaraju, E. Yang, R. Samy, H. Ng, W. Poh, A. Liew, M. Phoon, N. Van Rooijen, V. Chow. American Journal of Pathology, 2011
872 citations recorded by the source corpus.
Complications of acute respiratory distress syndrome (ARDS) are common among critically ill patients infected with highly pathogenic influenza viruses. Macrophages and neutrophils constitute the majority of cells recruited into infected lungs, and are associated with immunopathology in influenza pneumonia. We examined pathological manifestations in models of macrophage- or neutrophil-depleted mice challenged with sublethal doses of influenza A virus H1N1 strain PR8. Infected mice depleted of macrophages displayed excessive neutrophilic infiltration, alveolar damage, and increased viral load, later progressing into ARDS-like pathological signs with diffuse alveolar damage, pulmonary edema, hemorrhage, and hypoxemia. In contrast, neutrophil-depleted animals showed mild pathology in lungs. The brochoalveolar lavage fluid of infected macrophage-depleted mice exhibited elevated protein content, T1-α, thrombomodulin, matrix metalloproteinase-9, and myeloperoxidase activities indicating augmented alveolar-capillary damage, compared to neutrophil-depleted animals. We provide evidence for the formation of neutrophil extracellular traps (NETs), entangled with alveoli in areas of tissue injury, suggesting their potential link with lung damage. When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophils in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage.
Subfields: Immunology, Physiology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/792f24e36caced0a9c55879e329a8fe2a770becf
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Citations in the corpus
- Neutrophil extracellular traps (NETs): Double-edged swords of innate immunity (2012, background): “The role of NETs in fighting viral infections remains to be fully characterized, although these web structures may promote lung injury following influenza infection (7, 54, 55).”
- Neutrophil Extracellular Traps Directly Induce Epithelial and Endothelial Cell Death: A Predominant Role of Histones (2012, background): “NET structures and areas with tissue destruction adjacent to NET were observed in the LPS-treated mice as well as in other studies during influenza pneumonitis [68].”
- Neutrophil extracellular traps in COVID-19. (2020, background): “smoking-related lung disease (50), and, with particular relevance here, pathogen-induced acute lung injury and ARDS (14, 51, 53).”
- NETosis: how vital is it? (2013, background): “Here we describe at least 2 different mechanisms by which NETs are formed, including a suicide lytic NETosis and a live cell or vital NETosis.”