Redox processes are major regulators of leukotriene synthesis in neutrophils exposed to bacteria Salmonella typhimurium ; the way to manipulate neutrophil swarming.

Autor:	Golenkina EA; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia., Viryasova GM; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia., Galkina SI; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia., Kondratenko ND; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia., Gaponova TV; National Research Center for Hematology, Russia Federation Ministry of Public Health, Moscow, Russia., Romanova YM; Department of Genetics and Molecular Biology, Gamaleya National Research Centre of Epidemiology and Microbiology, Moscow, Russia., Lyamzaev KG; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.; The 'Russian Clinical Research Center for Gerontology' of the Ministry of Healthcare of the Russian Federation, Pirogov Russian National Research Medical University, Moscow, Russia., Chernyak BV; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia., Sud'ina GF; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Feb 07; Vol. 15, pp. 1295150. Date of Electronic Publication: 2024 Feb 07 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1295150
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Golenkina, Viryasova, Galkina, Kondratenko, Gaponova, Romanova, Lyamzaev, Chernyak and Sud’ina.)
Databáze:	MEDLINE
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