Your browser doesn't support javascript.
loading
Chemical Tools for Targeted Amplification of Reactive Oxygen Species in Neutrophils.
Reshetnikov, Viktor; Hahn, Jonas; Maueröder, Christian; Czegley, Christine; Munoz, Luis Enrique; Herrmann, Martin; Hoffmann, Markus H; Mokhir, Andriy.
Afiliação
  • Reshetnikov V; Department of Chemistry and Pharmacy, Organic Chemistry II, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Hahn J; Department of Internal Medicine 3 - Rheumatology and Immunology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Maueröder C; Cell Clearance in Health and Disease Lab, VIB Center for Inflammation Research, Ghent, Belgium.
  • Czegley C; Department of Biomedical Molecular Biology, Ghent university, Ghent, Belgium.
  • Munoz LE; Department of Internal Medicine 3 - Rheumatology and Immunology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Herrmann M; Department of Internal Medicine 3 - Rheumatology and Immunology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Hoffmann MH; Department of Internal Medicine 3 - Rheumatology and Immunology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Mokhir A; Department of Internal Medicine 3 - Rheumatology and Immunology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Front Immunol ; 9: 1827, 2018.
Article em En | MEDLINE | ID: mdl-30150984
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-targeted ROS enhancement can be achieved either by using conjugates of ROS amplifiers with ligands binding to receptors expressed on neutrophils (e.g., the GPI-anchored myeloid differentiation marker Ly6G or FPR) or by designing reagents activated by neutrophil function [e.g., phagocytic activity or enzymatic activity of neutrophil elastase (NE)]. Since binding of an artificial ligand to a receptor may trigger or inhibit priming of neutrophils the latter approach has a smaller potential for severe side effects and is probably better suitable for therapy. Here, we review current approaches for the use of ROS amplifiers and discuss their applicability for treatment. As an example, we suggest a possible design of neutrophil-specific ROS amplifiers, which are based on NE-activated ABPs.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Autoimunes / Compostos Ferrosos / Espécies Reativas de Oxigênio / Metalocenos / NADPH Oxidase 2 / Inflamação / Neoplasias / Neutrófilos Limite: Animals / Humans Idioma: En Revista: Front Immunol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Autoimunes / Compostos Ferrosos / Espécies Reativas de Oxigênio / Metalocenos / NADPH Oxidase 2 / Inflamação / Neoplasias / Neutrófilos Limite: Animals / Humans Idioma: En Revista: Front Immunol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Alemanha
...