Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarming
Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1295150/full |
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| author | Ekaterina A. Golenkina Galina M. Viryasova Svetlana I. Galkina Natalia D. Kondratenko Tatjana V. Gaponova Yulia M. Romanova Konstantin G. Lyamzaev Konstantin G. Lyamzaev Boris V. Chernyak Galina F. Sud’ina |
| author_facet | Ekaterina A. Golenkina Galina M. Viryasova Svetlana I. Galkina Natalia D. Kondratenko Tatjana V. Gaponova Yulia M. Romanova Konstantin G. Lyamzaev Konstantin G. Lyamzaev Boris V. Chernyak Galina F. Sud’ina |
| author_sort | Ekaterina A. Golenkina |
| collection | DOAJ |
| description | Neutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils surrounding pathogens. Here we describe a complex redox regulation that either stimulates or inhibits fMLP-induced leukotriene synthesis in an experimental model of neutrophils interacting with Salmonella typhimurium. The scavenging of mitochondrial reactive oxygen species by mitochondria-targeted antioxidants MitoQ and SkQ1, as well as inhibition of their production by mitochondrial inhibitors, inhibit the synthesis of leukotrienes regardless of the cessation of oxidative phosphorylation. On the contrary, antioxidants N-acetylcysteine and sodium hydrosulfide promoting reductive shift in the reversible thiol-disulfide system stimulate the synthesis of leukotrienes. Diamide that oxidizes glutathione at high concentrations inhibits leukotriene synthesis, and the glutathione precursor S-adenosyl-L-methionine prevents this inhibition. Diamide-dependent inhibition is also prevented by diphenyleneiodonium, presumably through inhibition of NADPH oxidase and NADPH accumulation. Thus, during bacterial infection, maintaining the reduced state of glutathione in neutrophils plays a decisive role in the synthesis of leukotriene B4. Suppression of excess leukotriene synthesis is an effective strategy for treating various inflammatory pathologies. Our data suggest that the use of mitochondria-targeted antioxidants may be promising for this purpose, whereas known thiol-based antioxidants, such as N-acetylcysteine, may dangerously stimulate leukotriene synthesis by neutrophils during severe pathogenic infection. |
| first_indexed | 2024-03-08T05:01:56Z |
| format | Article |
| id | doaj.art-07a0d956d4b640da871a328e8d97ec46 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T05:01:56Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-07a0d956d4b640da871a328e8d97ec462024-02-07T11:12:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.12951501295150Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarmingEkaterina A. Golenkina0Galina M. Viryasova1Svetlana I. Galkina2Natalia D. Kondratenko3Tatjana V. Gaponova4Yulia M. Romanova5Konstantin G. Lyamzaev6Konstantin G. Lyamzaev7Boris V. Chernyak8Galina F. Sud’ina9Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, RussiaNational Research Center for Hematology, Russia Federation Ministry of Public Health, Moscow, RussiaDepartment of Genetics and Molecular Biology, Gamaleya National Research Centre of Epidemiology and Microbiology, Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, RussiaThe “Russian Clinical Research Center for Gerontology” of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, RussiaNeutrophils play a primary role in protecting our body from pathogens. When confronted with invading bacteria, neutrophils begin to produce leukotriene B4, a potent chemoattractant that, in cooperation with the primary bacterial chemoattractant fMLP, stimulates the formation of swarms of neutrophils surrounding pathogens. Here we describe a complex redox regulation that either stimulates or inhibits fMLP-induced leukotriene synthesis in an experimental model of neutrophils interacting with Salmonella typhimurium. The scavenging of mitochondrial reactive oxygen species by mitochondria-targeted antioxidants MitoQ and SkQ1, as well as inhibition of their production by mitochondrial inhibitors, inhibit the synthesis of leukotrienes regardless of the cessation of oxidative phosphorylation. On the contrary, antioxidants N-acetylcysteine and sodium hydrosulfide promoting reductive shift in the reversible thiol-disulfide system stimulate the synthesis of leukotrienes. Diamide that oxidizes glutathione at high concentrations inhibits leukotriene synthesis, and the glutathione precursor S-adenosyl-L-methionine prevents this inhibition. Diamide-dependent inhibition is also prevented by diphenyleneiodonium, presumably through inhibition of NADPH oxidase and NADPH accumulation. Thus, during bacterial infection, maintaining the reduced state of glutathione in neutrophils plays a decisive role in the synthesis of leukotriene B4. Suppression of excess leukotriene synthesis is an effective strategy for treating various inflammatory pathologies. Our data suggest that the use of mitochondria-targeted antioxidants may be promising for this purpose, whereas known thiol-based antioxidants, such as N-acetylcysteine, may dangerously stimulate leukotriene synthesis by neutrophils during severe pathogenic infection.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1295150/fullneutrophilSalmonella typhimuriumleukotriene B4reactive oxygen speciesglutathioneneutrophil swarming |
| spellingShingle | Ekaterina A. Golenkina Galina M. Viryasova Svetlana I. Galkina Natalia D. Kondratenko Tatjana V. Gaponova Yulia M. Romanova Konstantin G. Lyamzaev Konstantin G. Lyamzaev Boris V. Chernyak Galina F. Sud’ina Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarming Frontiers in Immunology neutrophil Salmonella typhimurium leukotriene B4 reactive oxygen species glutathione neutrophil swarming |
| title | Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarming |
| title_full | Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarming |
| title_fullStr | Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarming |
| title_full_unstemmed | Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarming |
| title_short | Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium; the way to manipulate neutrophil swarming |
| title_sort | redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria salmonella typhimurium the way to manipulate neutrophil swarming |
| topic | neutrophil Salmonella typhimurium leukotriene B4 reactive oxygen species glutathione neutrophil swarming |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1295150/full |
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