Role of the respiratory burst in co-operative reduction in neutrophil survival by influenza A virus and Escherichia coli.
Influenza A virus (IAV)-induced impairment of neutrophil function or survival may be a cause of bacterial superinfection of IAV-infected subjects. This study was performed to determine the mechanism through which the combination of IAV and Escherichia coli co-operatively reduces neutrophil survival. Neutrophil binding of annexin-V and caspase-3 activation was significantly increased by either IAV or E. coli, supporting the concept that the micro-organisms accelerate neutrophil apoptosis. The anti-apoptotic agent granulocyte-macrophage colony stimulating factor (GM-CSF) did not improve, but further reduced, survival of neutrophils treated with IAV and E. coli. As addition of E. coli resulted in greater neutrophil uptake of IAV and greater neutrophil respiratory burst responses to IAV, this study tested whether respiratory burst activation by IAV and E. coli contributes to reducing neutrophil survival. The cell-permeant NADPH oxidase inhibitor, diphenylene iodonium, significantly increased survival of neutrophils treated with either E. coli alone or the combination of IAV and E. coli. In contrast, catalase, which is not cell permeant, did not alter survival of E. coli- and IAV-treated neutrophils. Azide enhanced neutrophil hydrogen peroxide responses to IAV and E. coli, and reduced survival of these cells. These results indicate that co-operative induction of intracellular respiratory burst responses by IAV and E.coli mediates the reduced neutrophil survival caused by these pathogens in vitro.
Engelich
Georg
G
Section of Hematology/Oncology, Department of Medicine and Pathology, Boston University School of Medicine, 650 Albany Street, Boston, MA 02218, USA.
White
Mitchell
M
Section of Hematology/Oncology, Department of Medicine and Pathology, Boston University School of Medicine, 650 Albany Street, Boston, MA 02218, USA.
Hartshorn
Kevan L
KL
Section of Hematology/Oncology, Department of Medicine and Pathology, Boston University School of Medicine, 650 Albany Street, Boston, MA 02218, USA.
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000150:complications* / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications* / Q000276:immunology; D009504:Neutrophils / Q000382:microbiology / Q000502:physiology* / Q000821:virology; D016897:Respiratory Burst / Q000502:physiology*; D015163:Superinfection / Q000209:etiology; D013997:Time Factors
D017304:Annexin A5; D004791:Enzyme Inhibitors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases