Eosinophils Preferentially Use Bromide to Generate Halogenating Agents

Mayeno, Arthur N.; Curran, A J; Roberts, Robert L.; Foote, Christopher S.

doi:10.1016/s0021-9258(18)83599-2

Cited by 136 publications

(43 citation statements)

References 56 publications

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“…Eosinophil peroxidase is a haloperoxide enzyme encoded for by the EPX gene and produces both HOBr and HOCl [437]. Even though it can produce HOCl, it preferentially chooses bromide over chloride to produce brominating agents even at physiological concentrations, when chloride is vastly more abundant [438].…”

Section: Group 17: the Halogensmentioning

confidence: 99%

The elements of life and medicines

Chellan

Sadler

2015

Phil. Trans. R. Soc. A.

192

117

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Which elements are essential for human life? Here we make an element-by-element journey through the periodic table and attempt to assess whether elements are essential or not, and if they are, whether there is a relevant code for them in the human genome. There are many difficulties such as the human biochemistry of several so-called essential elements is not well understood, and it is not clear how we should classify elements that are involved in the destruction of invading microorganisms, or elements which are essential for microorganisms with which we live in symbiosis. In general, genes do not code for the elements themselves, but for specific chemical species, i.e. for the element, its oxidation state, type and number of coordinated ligands, and the coordination geometry. Today, the biological periodic table is in a position somewhat similar to Mendeleev's chemical periodic table of 1869: there are gaps and we need to do more research to fill them. The periodic table also offers potential for novel therapeutic and diagnostic agents, based on not only essential elements, but also non-essential elements, and on radionuclides. Although the potential for inorganic chemistry in medicine was realized more than 2000 years ago, this area of research is still in its infancy. Future advances in the design of inorganic drugs require more knowledge of their mechanism of action, including target sites and metabolism. Temporal speciation of elements in their biological environments at the atomic level is a major challenge, for which new methods are urgently needed.

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Section: Group 17: the Halogensmentioning

confidence: 99%

The elements of life and medicines

Chellan

Sadler

2015

Phil. Trans. R. Soc. A.

192

117

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“…Among them, EPO plays the crucial role in killing helminth [51]. It can catalyze the peroxidative oxidation of halides and thiocyanate present in the plasma together with hydrogen peroxide (H 2 O 2 ) generated by dismutation of superoxide produced during respiratory burst [14][15][16]. High level of the enzyme complex that generates superoxide is expressed in Eosinophils, and superoxide anions are produced in response to helminth-derived immunomodulating agents.…”

Section: Discussionmentioning

confidence: 99%

“…High percentage of eosinophils, recruited from the circulation into the central nervous system [7], as the primary pathological change in eosinophilic meningitis, is thought to contribute to tissue in ammatory responses and host defense in helminthic infections [11]. High level of the enzyme complex is expressed and released in the granule matrix of eosinophils, such as eosinophil peroxidase (EPO) [12,13] which is associated with helminthic killing, using the peroxidative oxidation and hydrogen peroxide (H 2 O 2 ) generated by dismutation of superoxide produced during respiratory burst [14][15][16]. In contrast, helminthic worms, parasitizing with high level of eosinophils, have evolved to attenuate eosinophil-mediated tissue in ammatory responses for their survival [11].…”

Section: Introductionmentioning

confidence: 99%

Up-Regulated Galectin-1 in Angiostrongylus Cantonensis L5 Reduces Body Fat and Increases Oxidative Stress Tolerance

Sun¹,

Yan²,

Qiao³

et al. 2021

Preprint

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Background: Angiostrongylus cantonensis L5, parasitizing in human cerebrospinal fluid, leads to eosinophilic meningitis, which is attributed to tissue inflammatory responses caused primarily by high percentage of eosinophils. Eosinophils are also involved in helminthic killing, using the peroxidative oxidation and hydrogen peroxide (H2O2) generated by dismutation of superoxide produced during respiratory burst. In contrast, helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival. In previous study, we have demonstrated the extracellular function of Acan-Gal-1 in inducing the apoptosis of macrophages. And here, the intracellular functions of Acan-Gal-1 were investigated with the aim to further reveal the mechanism of A. cantonensis L5 worms surviving in the central nervous system of human from inflammatory responses. Methods: Bioinformatics were used to analyse the structural characterisation of Acan-Gal-1; qRT-PCR and microinjection were performed to detect the expression patterns of Acan-gal-1; microinjection was performed to construct transgenic worms; oxidative stress assay and Oil Red O fat staining were used to determine the functions of Acan-Gal-1.Results: The results showed that Acan-Gal-1 was expressed ubiquitously and mainly localized in cuticle, and it was up-regulated in both L5 and adult worm. N2 worms expressing pCe-Acan-gal-1::Acan-gal-1::rfp, with lipid deposition reduced, were significantly resistant to oxidative stress. lec-1 mutant worms, with lipid deposition increased, showed susceptible to oxidative stress, and this phenotype could be rescued by expressing pCe-Acan-gal-1::Acan-gal-1::rfp. And fat-6;fat-7 double-mutant worms expressing pCe-Acan-gal-1::Acan-gal-1::rfp showed no significant changes in oxidative stress tolerance.Conclusion: In C. elegans worms, up-regulated Acan-Gal-1 plays a defensive role against damage due to oxidative stress for worm survival through reducing fat deposition. And this might indicate the mechanism of A. cantonensis L5 worms, with Acan-Gal-1 up-regulated, surviving in the central nervous system of human from immune attack of Eosinophil.

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“…The functional role of EPO is associated with helminthic killing [44]. EPO catalyzes the peroxidative oxidation of halides and thiocyanate present in the plasma together with hydrogen peroxide (H 2 O 2 ) generated by dismutation of superoxide produced during respiratory burst [11][12][13]. Eosinophils, the robust producers of extracellular superoxide due to expression of high level of the enzyme complex that generates superoxide [7], produce superoxide anions in response to helminth-derived cysteine proteases [45].…”

Section: Discussionmentioning

confidence: 99%

“…EPO is associated with helminthic killing, using the peroxidative oxidation and hydrogen peroxide (H 2 O 2 ) generated by dismutation of superoxide produced during respiratory burst [11][12][13]. In contrast, residing in the host with high level of eosinophils, helminthic worms have evolved to attenuate eosinophil-mediated tissue in ammatory responses for their survival in hosts [8].…”

Section: Introductionmentioning

confidence: 99%

Down-regulated RPS-30 in Angiostrongylus cantonensis L5 plays a defensive role against damage due to oxidative stress

Sun

Yan

Shi

et al. 2020

Preprint

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Background: Eosinophilic meningitis, caused by Angiostrongylus cantonensis L5, is mainly attributed to the Eosinophils, which contribute to tissue inflammatory responses in helminthic infections. Eosinophils are associated with helminthic killing, using the peroxidative oxidation and hydrogen peroxide (H2O2) generated by dismutation of superoxide produced during respiratory burst. In contrast, residing in the host with high level of eosinophils, helminthic worms have evolved to attenuate eosinophil-mediated tissue inflammatory responses for their survival in hosts. Our previous study demonstrated that the expression of Acan-rps-30 was significantly down-regulated in A. cantonensis L5 worms, which reside in the cerebrospinal fluid with high level of Eosinophils. Acan-RPS-30, a homologous protein of human Fau, which plays a pro-apoptotic regulatory role, may function in protecting worms from oxidative stress.Methods: RACE, genome Walking, bioinformatics were used to isolate and analyse the structural characterisation of Acan-RPS-30; qRT-PCR and microinjection was performed to detect the expression patterns of Acan-rps-30; feeding RNAi was used to ced-3 knock-down; microinjection was performed to construct transgenic worms; oxidative stress assay was used to determine the functions of Acan-RPS-30.Results: Our results showed that Acan-RPS-30 consisted of 130 amino acids, and was grouped into Clade V with C. elegans in phylogenetic analysis. It was expressed ubiquitously in worms and was down-regulated in both L5 and adult A. cantonensis. Worms expressing pCe-rps30::Acan-rps-30::rfp, with the refractile “button-like” apoptotic corpses, were susceptible to oxidative stress. Apoptosis genes ced-3 and ced-4 were both up-regulated in the transgenic worms. And the phenotype susceptible to oxidative stress could be converted with ced-3 defective mutation and RNAi. rps-30- /- mutant worms were resistant to oxidative stress, with ced-3 and ced-4 were both down-regulated. And the oxidative stress resistance phenotype could be rescued and inhibited by expressing pCe-rps30::Acan-rps-30::rfp in rps-30- /- mutant worms. Conclusion: In C. elegans worms, down-regulated RPS-30 plays a defensive role against damage due to oxidative stress for worm survival by regulating ced-3 down-regulated. And this might indicate the mechanism of A. cantonensis L5 worms, with Acan-RPS-30 down-regulated, surviving in the central nervous system of human from immune attack of Eosinophil.

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Eosinophils Preferentially Use Bromide to Generate Halogenating Agents

Cited by 136 publications

References 56 publications

The elements of life and medicines

The elements of life and medicines

Up-Regulated Galectin-1 in Angiostrongylus Cantonensis L5 Reduces Body Fat and Increases Oxidative Stress Tolerance

Down-regulated RPS-30 in Angiostrongylus cantonensis L5 plays a defensive role against damage due to oxidative stress

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