The pivotal role of glutathione reductase in host defense
against Gram-negative bacteria [2011](IR92)
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(Memo Item created on May 10, 2012 03:59 PM)
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The pivotal role of glutathione reductase in host defense
against Gram-negative bacteria
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J Immunol April 2011 186 (Meeting Abstract
Supplement) 111.25
The Journal of
Immunology, 2011, 186, 111.25
Copyright © 2011 by The American
Association of Immunologists, Inc.
111.25
The pivotal role of glutathione reductase in host defense
against Gram-negative bacteria
Jing Yan,1,2Xiaomei Meng,1Lyn
Wancket,3Katherine Lintner,1Haiwa Wu,1Leif Nelin,1,4Bernadatte Chen,1,4Charles
Smith,5Lynette Rogers,1,4 and Yusen Liu1,3,4
1Center for Perinatal Research, Research
Institute at Nationwide Children's Hospital, Columbus, OH 2State Key Laboratory
of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou,
China 3Department of Veterinary Biosciences, Ohio State University College of
Veterinary Biosciences, Columbus, OH 4Department of Pediatrics, Ohio State
University College of Medicine, Columbus, OH 5Center for Developmental
Therapeutics, Seattle Children’s Hospital Research Institute, Seattle, WA
Glutathione reductase (Gsr) is an enzyme
that reduces glutathione disulfide to the sulfhydryl form, a major cellular
antioxidant. Oxidative burst plays an important role in pathogen killing and
initiation of inflammation. Proper redox regulation is crucial for balancing
effective pathogen elimination and host preservation. We tested the hypothesis
that Gsr plays a critical role in host defense by comparing wildtype (WT) and
Gsr- mice after E. coli infection. Compared to WT mice, Gsr- mice exhibited
substantially higher mortality, associated with greater bacterial burden,
cytokine storm, and striking histological abnormalities. Surprisingly, Gsr-
mice displayed increased resistance to LPS. While Gsr- mice exhibited defects
in phagocyte mobilization, there appeared no substantial defects in either cell
signaling or cytokine production in Gsr- macrophages. The role of Gsr in
phagocytic oxidative burst was assessed by both flow cytometry and
bioluminescence imaging. The oxidative burst in WT neutrophils after PMA
stimulation was sustained for more than 30 min, while oxidative burst was very
transient in Gsr- cells (<5 min). Likewise, oxidative burst after E. coli
infection was also significantly weaker in the Gsr- neutrophils. Thus, Gsr plays a critical role in host defense against
bacterial infection by regulating various immune functions, including
facilitation of bacterial killing via sustaining oxidative burst in phagocytes,
through maintenance of a delicate redox balance.
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