Macrophage-derived peroxynitrite diffusion and toxicity to Trypanosoma cruzi

We studied the capacity of macrophage-derived peroxynitrite to diffuse into and exert cytotoxicity against Trypanosoma cruzi, the causative agent of Chagas’ disease. In two types of macrophage– T. cruzi co-cultures, one with a fixed separation distance between source and target cells, and another in...

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Published in:Archives of biochemistry and biophysics 2004-12, Vol.432 (2), p.222-232
Main Authors: Alvarez, María Noel, Piacenza, Lucía, Irigoín, Florencia, Peluffo, Gonzalo, Radi, Rafael
Format: Article
Language:English
Subjects:
Animals
Cell Communication - drug effects
Cell Communication - physiology
Cell Line
Cell Proliferation - drug effects
Cell Respiration - drug effects
Cell Respiration - physiology
Coculture Techniques - methods
Diffusion
Free radicals
iNOS
Macrophage
Macrophages - secretion
Mice
NADPH oxidase
Nitric oxide
Oxidants - pharmacology
Oxidation
Oxidation-Reduction - drug effects
Oxygen - metabolism
Peroxynitrite
Peroxynitrous Acid - biosynthesis
Peroxynitrous Acid - chemistry
Peroxynitrous Acid - pharmacology
Reactive Oxygen Species - metabolism
Superoxide
Trypanosoma cruzi
Trypanosoma cruzi - drug effects
Trypanosoma cruzi - physiology
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Summary:We studied the capacity of macrophage-derived peroxynitrite to diffuse into and exert cytotoxicity against Trypanosoma cruzi, the causative agent of Chagas’ disease. In two types of macrophage– T. cruzi co-cultures, one with a fixed separation distance between source and target cells, and another involving cell-to-cell interactions, peroxynitrite resulted in significant oxidation of intracellular dihydrorhodamine and inhibition of [ 3H]thymidine incorporation in T. cruzi, which were not observed by superoxide or nitric oxide alone. The effects were attenuated in the presence of bicarbonate, in agreement with the extracellular consumption of peroxynitrite by its fast reaction with CO 2. However, studies using different T. cruzi densities, which allow to modify average diffusion distances of exogenously added peroxynitrite to target cells, indicate that at distances
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2004.09.015