Liuluan Zhu1,2, Lu Liu3, Yue Zhang1,2, Lin Pu4, Jingyuan Liu4, Xingwang Li5, Zhihai Chen5, Yu Hao1,2, Beibei Wang1,2, Junyan Han1,2, Guoli Li1,2, Shuntao Liang1,2, Haofeng Xiong4, Hong Zheng6, Ang Li4, Jianqing Xu3, Hui Zeng1,2. 1. Institute of Infectious Diseases, Capital Medical University, China. 2. Beijing Key Laboratory of Emerging Infectious Diseases, China. 3. Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China. 4. Intensive Care Unit, Capital Medical University, China. 5. The National Clinical Key Department of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, China. 6. Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, Pennsylvania.
Abstract
Background: Most patients with severe infection with influenza A virus (IAV) progress to acute respiratory distress syndrome and even multiple organ dysfunction syndrome (MODS). Neutrophil extracellular traps (NETs) can be induced by pathogens and are responsible for immune tissue damage. We conducted a prospective study on the production and effects of NETs in H7N9 and H1N1 patients. Methods: We investigated NET production in plasma and supernatant of cultured neutrophils by measuring cell-free deoxyribonucleic acid (DNA) and myeloperoxidase (MPO)-DNA complexes with PicoGreen dye and enzyme-linked immunosorbent assay methods, respectively. We also observed NET structure by immunofluorescence staining. Results: We found that patients with severe influenza showed elevated plasma NET level on the day of admission. Neutrophils from these patients showed higher capacity to release MPO-DNA complex in response to interleukin-8 or lipopolysaccharide stimulation. We also found that NETs from H7N9 and H1N1 patients increased the permeability of alveolar epithelial cells, and, consequently, NET production was positively correlated with acute physiology and chronic health evaluation (APACHE) II score and MODS. Conclusions: These data indicate that high level of NETs contributes to lung injury and is correlated with severity of disease. Thus, NETs might be a key factor to predict the poor prognosis in IAV patients.
Background: Most patients with severe infection with influenza A virus (IAV) progress to acute respiratory distress syndrome and even multiple organ dysfunction syndrome (MODS). Neutrophil extracellular traps (NETs) can be induced by pathogens and are responsible for immune tissue damage. We conducted a prospective study on the production and effects of NETs in H7N9 and H1N1patients. Methods: We investigated NET production in plasma and supernatant of cultured neutrophils by measuring cell-free deoxyribonucleic acid (DNA) and myeloperoxidase (MPO)-DNA complexes with PicoGreen dye and enzyme-linked immunosorbent assay methods, respectively. We also observed NET structure by immunofluorescence staining. Results: We found that patients with severe influenza showed elevated plasma NET level on the day of admission. Neutrophils from these patients showed higher capacity to release MPO-DNA complex in response to interleukin-8 or lipopolysaccharide stimulation. We also found that NETs from H7N9 and H1N1patients increased the permeability of alveolar epithelial cells, and, consequently, NET production was positively correlated with acute physiology and chronic health evaluation (APACHE) II score and MODS. Conclusions: These data indicate that high level of NETs contributes to lung injury and is correlated with severity of disease. Thus, NETs might be a key factor to predict the poor prognosis in IAV patients.
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