Glutathione reductase facilitates host defense by sustaining phagocytic oxidative burst and promoting the development of neutrophil extracellular traps (172.3)
| Autor: | Yusen Liu, Jing Yan, Xiaomei Meng, Lyn Wancket, Katherine Lintner, Leif Nelin, Bernadette Chen, Kevin Francis, Charles Smith, Lynette Rogers |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:172.3-172.3 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.188.supp.172.3 |
| Popis: | Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione. Since Gsr has been implicated in the oxidative burst in human PMN, we hypothesized that Gsr-null mice would exhibit marked defects during the immune response against bacterial challenge. We report here that Gsr-null mice exhibited enhanced susceptibility to E. coli challenge, indicated by dramatically increased bacterial burden, cytokine storm, striking histological abnormalities, and substantially elevated mortality. Examination of the bactericidal functions of the neutrophils from Gsr-null mice in vitro revealed impaired phagocytosis and defective bacterial killing activities. Although Gsr catalyzes the regeneration of glutathione, a major cellular antioxidant, Gsr-null neutrophils paradoxically produced far less reactive oxygen species both ex vivo and in vivo. Unlike wildtype neutrophils that exhibited a sustained oxidative burst upon activation, Gsr-null neutrophils displayed a very transient oxidative burst associated with compromised hexose monophosphate shunt. Likewise, Gsr-null neutrophils also exhibited an attenuated oxidative burst upon encountering E. coli. Moreover, Gsr-null neutrophils displayed a marked impairment in the formation of neutrophil extracellular traps, a bactericidal mechanism which operates after neutrophil death. Thus, Gsr-mediated redox regulation is crucial for bacterial clearance during host defense against massive bacterial challenge. |
| Databáze: | OpenAIRE |
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