Chemical Tools for Targeted Amplification of Reactive Oxygen Species in Neutrophils

Frontiers in Immunology
Viktor ReshetnikovAndriy Mokhir

Abstract

A number of chemical compounds are known, which amplify the availability of reactive oxygen species (ROS) in neutrophils both in vitro and in vivo. They can be roughly classified into NADPH oxidase 2 (NOX2)-dependent and NOX2-independent reagents. NOX2 activation is triggered by protein kinase C agonists (e.g., phorbol esters, transition metal ions), redox mediators (e.g., paraquat) or formyl peptide receptor (FPR) agonists (e.g., aromatic hydrazine derivatives). NOX2-independent mechanisms are realized by reagents affecting glutathione homeostasis (e.g., l-buthionine sulfoximine), modulators of the mitochondrial respiratory chain (e.g., ionophores, inositol mimics, and agonists of peroxisome proliferator-activated receptor γ) and chemical ROS amplifiers [e.g., aminoferrocene-based prodrugs (ABPs)]. Since a number of inflammatory and autoimmune diseases, as well as cancer and bacterial infections, are triggered or enhanced by aberrant ROS production in neutrophils, it is tempting to use ROS amplifiers as drugs for the treatment of these diseases. However, since the known reagents are not cell specific, their application for treatment likely causes systemic enhancement of oxidative stress, leading to severe side effects. Cell-ta...Continue Reading

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Citations

Jan 29, 2020·Antioxidants & Redox Signaling·Irundika H K DiasHelen R Griffiths
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Mar 23, 2021·Frontiers in Immunology·Michele Fresneda AlarconHelen Louise Wright
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May 25, 2021·Chemical Society Reviews·Yuxuan XiongXiangliang Yang
Jun 22, 2021·Frontiers in Immunology·Alexia Dumas, Ulla G Knaus
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Igor A SchepetkinMark T Quinn

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Methods Mentioned

BETA
protein folding
PMA
fluorescence imaging

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