Production of hydrogen peroxide by peripheral blood monocytes and specific macrophages during experimental infection with <i>Trypanosoma cruzi</i> in vivo

Melo, Rossana C. N.; Fabrino, Daniela Leite; D’Avila, Heloísa; Teixeira, Henrique Couto; Ferreira, Ana Paula

doi:10.1016/s1065-6995(03)00173-2

Cited by 47 publications

(41 citation statements)

References 35 publications

(59 reference statements)

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“…During the acute phase of infection, the presence of the parasite induces a rapid increase in the production, maturation, and activation of monocytes/macrophages in an attempt to control its replication 6 . In vivo, these cells secrete hydrogen peroxide and nitric oxide (NO) when in contact with the parasite 7,8 .…”

Section: Palavras-chavesmentioning

confidence: 99%

Production of cytokine and chemokines by human mononuclear cells and whole blood cells after infection with Trypanosoma cruzi

Rezende-Oliveira

Sarmento

Rodrigues

2012

Rev. Soc. Bras. Med. Trop.

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INTRODUCTION: The innate immune response is the first mechanism of protection against Trypanosoma cruzi, and the interaction of inflammatory cells with parasite molecules may activate this response and modulate the adaptive immune system. This study aimed to analyze the levels of cytokines and chemokines synthesized by the whole blood cells (WBC) and peripheral blood mononuclear cells (PBMC) of individuals seronegative for Chagas disease after interaction with live T. cruzi trypomastigotes. METHODS: IL-12, IL-10, TNF-α, TGF-β, CCL-5, CCL-2, CCL-3, and CXCL-9 were measured by ELISA. Nitrite was determined by the Griess method. RESULTS: IL-10 was produced at high levels by WBC compared with PBMC, even after incubation with live trypomastigotes. Production of TNF-α by both PBMC and WBC was significantly higher after stimulation with trypomastigotes. Only PBMC produced significantly higher levels of IL-12 after parasite stimulation. Stimulation of cultures with trypomastigotes induced an increase of CXCL-9 levels produced by WBC. Nitrite levels produced by PBMC increased after the addition of parasites to the culture. CONCLUSIONS: Surface molecules of T. cruzi may induce the production of cytokines and chemokines by cells of the innate immune system through the activation of specific receptors not evaluated in this experiment. The ability to induce IL-12 and TNF-α contributes to shift the adaptive response towards a Th1 profile.

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Section: Palavras-chavesmentioning

confidence: 99%

Production of cytokine and chemokines by human mononuclear cells and whole blood cells after infection with Trypanosoma cruzi

Rezende-Oliveira

Sarmento

Rodrigues

2012

Rev. Soc. Bras. Med. Trop.

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“…These reactive nitrogen species result in protein tyrosine nitration (3NT), which is widely recognized as a hallmark of nitrosative stress (32). In animals with Chagas' disease, increased levels of O 2 ⅐ Ϫ formation due to an oxidative burst of activated macrophages (25,26) and an increased leakage of electrons from the respiratory chain to O 2 (38) have been documented. ⅐ NO synthesis by iNOS during the inflammatory response against infectious agents represents a host defense system (36) and is documented for mice infected by T. cruzi (13,27).…”

Section: Vol 16 2009 Indicators Of Inflammation In Chagas' Disease 663mentioning

confidence: 99%

Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease

Dhiman

Estrada-Franco

Pando

et al. 2009

Clin Vaccine Immunol

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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 cruzi-specific antibodies. We identified 121 subjects who were seropositive for T. cruzi-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-nitrotyrosine [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 (O 2 ⅐ ؊ source) and nitrate/nitrite contents (denotes iNOS activation and ⅐ 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 ⅐ NO and O 2 ⅐ ؊ concentrations contributes to protein nitration. Overall, our data demonstrate that T. cruzi-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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“…Several investigators have used in vitro assay systems or animal models and demonstrated that T. cruzi-mediated macrophage activation result in increased levels of superoxide formation by the NADPH oxidase-dependent respiratory burst. 20,34,35 Besides oxidative stress of inflammatory origin, chagasic host exhibits compromised mitochondrial respiratory chain efficiency in the heart 17,18 that contributes to a substantial increase in ROS generation in cardiomyocytes. Increased expression of XOD (superoxide source), as noted in this study, suggest that endothelial ROS may also be produced in chagasic animals.…”

Section: Dhiman Et Almentioning

confidence: 99%

Enhanced Nitrosative Stress during Trypanosoma cruzi Infection Causes Nitrotyrosine Modification of Host Proteins

Dhiman

Nakayasu

Madaiah

et al. 2008

The American Journal of Pathology

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Oxidative/nitrosative stress may be important in the pathology of Chagas' disease. Experimental animals infected by Trypanosoma cruzi showed an early rise in myocardial and peripheral protein-3-nitrotyrosine (3NT) and protein-carbonyl formation that persisted during the chronic stage of disease. In comparison, experimental chronic ethanol-induced cardiomyopathy was slow to develop and presented with a moderate increase in oxidative stress and minimal to no nitrosative stress after long-term alcohol feeding of animals. The oxidative stress in both chagasic animals and animals with ethanol-induced cardiomyopathy correlated with the persistence of reactive oxygen species-producing inflammatory intermediates. Protein-3NT formation in T. cruzi-infected animals was associated with enhanced nitric oxide expression (inferred by nitrite/nitrate levels) and myeloperoxidase activity, suggesting that both peroxynitrite-and myeloperoxidase-mediated pathways contribute to increased protein nitration in Chagas' disease. We used one-and two-dimensional gel electrophoresis and Western blot analysis to identify disease-specific plasma proteins that were 3NT-modified in T. cruzi-infected animals. Nitrated protein spots (56 in total) were sequenced by matrix-assisted laser desorption ionization/time of flight mass spectrometry and liquid chromatography-tandem mass spectrometry and identified by a homology search of public databases. Clustering of 3NT-modified proteins according to their functional characteristics revealed that the nitration of immunoglobulins, apolipoprotein isoforms, and other proteins might perturb their functions and be important in the pathology of Chagas' disease. We also showed that nitrated peptides derived from titin and ␣-actin were released into the plasma of patients with Chagas' disease. Such modified proteins may be useful biomarkers of Chagas' disease.

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Production of hydrogen peroxide by peripheral blood monocytes and specific macrophages during experimental infection with Trypanosoma cruzi in vivo

Cited by 47 publications

References 35 publications

Production of cytokine and chemokines by human mononuclear cells and whole blood cells after infection with Trypanosoma cruzi

Production of cytokine and chemokines by human mononuclear cells and whole blood cells after infection with Trypanosoma cruzi

Increased Myeloperoxidase Activity and Protein Nitration Are Indicators of Inflammation in Patients with Chagas' Disease

Enhanced Nitrosative Stress during Trypanosoma cruzi Infection Causes Nitrotyrosine Modification of Host Proteins

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