Peroxynitrite, a potent macrophage-derived oxidizing cytotoxin to combat invading pathogens

Prolo, C; Alvarez, MN; Radi, R

HERO ID

2232247

Reference Type

Journal Article

Year

2014

Language

English

PMID

24281946

HERO ID 2232247
In Press No
Year 2014
Title Peroxynitrite, a potent macrophage-derived oxidizing cytotoxin to combat invading pathogens
Authors Prolo, C; Alvarez, MN; Radi, R
Journal BioFactors
Volume 40
Issue 2
Page Numbers 215-225
Abstract Macrophages are among the first cellular actors facing the invasion of microorganisms. These cells are able to internalize pathogens and destroy them by means of toxic mediators, many of which are produced enzymatically and have strong oxidizing capacity. Indeed, macrophages count on the NADPH oxidase complex activity, which is triggered during pathogen invasion and leads to the production of superoxide radical inside the phagosome. At the same time, the induction of nitric oxide synthase results in the production of nitric oxide in the cytosol which is able to readily diffuse to the phagocytic vacuole. Superoxide radical and nitric oxide react at diffusion controlled rates with each other inside the phagosome to yield peroxynitrite, a powerful oxidant capable to kill micro-organisms. Peroxynitrite toxicity resides on oxidations and nitrations of biomolecules in the target cell. The central role of peroxynitrite as a key effector molecule in the control of infections has been proven in a wide number of models. However, some microorganisms and virulent strains adapt to survive inside the potentially hostile oxidizing microenvironment of the phagosome by either impeding peroxynitrite formation or rapidly detoxifying it once formed. In this context, the outcome of the infection process is a result of the interplay between the macrophage-derived oxidizing cytotoxins such as peroxynitrite and the antioxidant defense machinery of the invading pathogens. © 2013 BioFactors, 2013.
Doi 10.1002/biof.1150
Pmid 24281946
Wosid WOS:000334690900005
Is Certified Translation No
Dupe Override No
Is Public Yes
Language Text English
Keyword free radicals; peroxynitrite; superoxide; nitric oxide; oxidants