TY - JOUR
T1 - Increased myeloperoxidase activity and protein nitration are indicators of inflammation in patients with chagas' disease
AU - Dhiman, Monisha
AU - Estrada-Franco, Jose Guillermo
AU - Pando, Jasmine M.
AU - Ramirez-Aguilar, Francisco J.
AU - Spratt, Heidi
AU - Vazquez-Corzo, Sara
AU - Perez-Molina, Gladys
AU - Gallegos-Sandoval, Rosa
AU - Moreno, Roberto
AU - Garg, Nisha Jain
PY - 2009/5
Y1 - 2009/5
N2 - In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n = 1,481) originating from Chiapas, Mexico, for Trypanosoma crwzi-specific antibodies. We identified 121 subjects who were seropositive for T. crwzi'-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitroty- rosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (OO 2 ̇- source) and nitrate/nitrite contents (denotes iNOS activation and 'NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological 'NO and O 2 ̇-p concentrations contributes to protein nitration. Overall, our data demonstrate that T. crwzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies capable of suppressing MPO activity may be useful in controlling the inflammation and oxidative/nitrosative pathology in chagasic cardiomyopathy.
AB - In this study, we investigated whether inflammatory responses contribute to oxidative/nitrosative stress in patients with Chagas' disease. We used three tests (enzyme-linked immunosorbent assay, immuno-flow cytometry, and STAT-PAK immunochromatography) to screen human serum samples (n = 1,481) originating from Chiapas, Mexico, for Trypanosoma crwzi-specific antibodies. We identified 121 subjects who were seropositive for T. crwzi'-specific antibodies, a finding indicative of an 8.5% seroprevalence in the rural population from Chiapas. Seropositive and seronegative subjects were examined for plasma levels of biomarkers of inflammation, i.e., myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), and xanthine oxidase (XOD), as well as for oxidative (advanced oxidation protein products [AOPPs]) and nitrosative (3-nitroty- rosine [3NT]) biomarkers. The seropositive subjects exhibited a significant increase in MPO activity and protein level, the indicator of neutrophil activation. Subsequently, a corresponding increase in AOPP contents, formed by MPO-dependent hypochlorous acid and chloramine formation, was noted in seropositive subjects. The plasma level of 3NT was significantly increased in seropositive subjects, yet we observed no change in XOD activity (OO 2 ̇- source) and nitrate/nitrite contents (denotes iNOS activation and 'NO production), which implied that direct peroxynitrite formation does not contribute to increased nitrosative damage in chagasic subjects. Instead, a positive correlation between increased MPO activity and protein 3NT formation was observed, which suggested to us that MPO-dependent formation of nitrylchloride that occurs in the presence of physiological 'NO and O 2 ̇-p concentrations contributes to protein nitration. Overall, our data demonstrate that T. crwzi-induced neutrophil activation is pathological and contributes to MPO-mediated collateral protein oxidative and nitrosative damage in human patients with Chagas' disease. Therapies capable of suppressing MPO activity may be useful in controlling the inflammation and oxidative/nitrosative pathology in chagasic cardiomyopathy.
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U2 - 10.1128/CVI.00019-09
DO - 10.1128/CVI.00019-09
M3 - Article
C2 - 19297613
AN - SCOPUS:66849126219
SN - 1556-6811
VL - 16
SP - 660
EP - 666
JO - Clinical and Vaccine Immunology
JF - Clinical and Vaccine Immunology
IS - 5
ER -