Nitric oxide in parasitic infections

Brunet, Laura Rosa

doi:10.1016/s1567-5769(01)00090-x

Cited by 204 publications

(147 citation statements)

References 90 publications

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“…It has been observed that the absence of NO during acute schistosomiasis leads to increased hepatic damage characterized by hepatocyte apoptosis and increased hepatocellular enzyme release 11 . These findings are supportive of the proposed protective role for NO in preventing hepatocyte damage induced by TNF-alpha and oxygen radicals 12 . On the other hand, NO seems to be pivotal in the regulation of granulomatous responses to liver involvement of the S. mansoni infection 13,14 .…”

Section: Introductionsupporting

confidence: 82%

Nitric oxide monocyte production levels in patients with the hepatosplenic form of Scistosoma mansoni infection who underwent splenectomy, ligature of the left gastric vein and auto implantation of spleen tissue in the major omentum

Brandt¹,

Leite²,

Manhaes-de-Castro³

et al. 2006

Acta Cir. Bras.

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Nitric oxide monocyte production levels in patients with the hepatosplenic form of Scistosoma mansoni infection 4 -ORIGINAL ARTICLE Nitric oxide monocyte production levels in patients with the hepatosplenic form of Scistosoma mansoni infection who underwent splenectomy, ligature of the left gastric vein and auto implantation of spleen tissue in the major omentum 1 Níveis de óxido nítrico produzidos por monócitos em portadores de esquistossomose hepatoesplênica que se submeteram a esplenectomia, ligadura da veia gástrica esquerda e auto-implante de tecido esplênico no omento maior ABSTRACT Purpose:To measure the levels of NO production by monocytes in patients with the hepatosplenic form of schistosomiasis mansoni who underwent splenectomy, ligature of the left gastric vein and auto implantation of spleen tissue in the major omentum. Methods: Four groups of volunteers were enrolled in the investigation: G1 -12 patients with S. mansoni infection in its hepatosplenic form without any kind of treatment (SMH); G2 -13 SMH patients who underwent medical treatment and portal hypertension decompression -splenectomy and ligature of the left gastric vein (SMH/SLGV); G3 -19 patients similar to the later group, but additionally received auto implantation of spleen morsels in the major omentum (SMH/SLGV/AI); and G4 -15 individuals with no S. mansoni infection coming from the same geographical area and presenting similar socio economical status (CG). Nitrite production by monocytes was determined by a standard Griess reaction adapted to microplates. The results were presented by mean ± SD for each group. Significant differences in NO production by monocytes were determined by Tukey-Kramer multicomparisons test. Probability values of 0.05 were considered significant. Results: Patients from G1 (SMH) showed lower level of NO production by monocytes (5.28 ± 1.28µmol/ml). Patients from G2 (SMH/SLGV) showed similar results (6.67 ± 0.44µmol/ml -q = 2.681 p > 0.05). Individuals of G4 (CG) showed higher level of NO production by monocytes (8.19 ± 2.74µmol/ml). Patients from G3 (SMH/SGLV/AI) showed similar NO production by PBMC as compared to individuals of G4 (CG) -(7.41 ± 1.65µmol/ml -q = 1.615 p > 0.05). The volunteers from G4 (CG) and G3 (SMH/SLGV/AI) showed significantly greater levels of NO production by monocytes as compared to those from G1 (SMH) -(q = 5.837 p < 0.01, and q = 4.285 p < 0.05). Conclusion: Collectively, the results point to a restoration of NO normal production by monocytes in SHM patients who underwent medical and surgical treatments, especially in those who had received auto implantation of spleen tissue in the major omentum after splenectomy and ligature of the left gastric vein. The data gives further support to the hypothesis that this additional procedure is important in the restoration of the immune response of these patients, since NO synthesis by the monocytes correlates with protective immunity against infection; thus, protecting them against overwhelming post splenectomy infection. Key words: Schistoso...

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Section: Introductionsupporting

confidence: 82%

Nitric oxide monocyte production levels in patients with the hepatosplenic form of Scistosoma mansoni infection who underwent splenectomy, ligature of the left gastric vein and auto implantation of spleen tissue in the major omentum

Brandt¹,

Leite²,

Manhaes-de-Castro³

et al. 2006

Acta Cir. Bras.

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“…To survive and propagate within the not so conducive environment of macrophages, the protozoan parasite Leishmania cleverly inhibits several macrophage functions, including production of reactive nitrogen intermediates (3,46). Mammalian cells require only 2.0 lM DAF-2DA for measurement of intracellular NO (28,29), whereas Leishmania parasites need a 20 fold higher concentration of DAF-2DA.…”

Section: Parasitized Macrophages Had Decreased Levels Of No That Was mentioning

confidence: 99%

Monitoring of intracellular nitric oxide in leishmaniasis: Its applicability in patients with visceral leishmaniasis

et al. 2010

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Nitric oxide (NO) has been demonstrated to be a principal effector molecule responsible for mediating intracellular killing of Leishmania parasites, the causative organism of leishmaniasis. As measurement of intracellular NO remains a challenge to biologists, we have developed a flow cytometric approach to perform real time biological detection of NO within Leishmania parasites and parasitized macrophages using a membrane permeable derivative of diaminofluorescein [4,5-diaminofluorescein diacetate (DAF-2DA)]. Initially, assay optimization was performed in Leishmania donovani promastigotes, assay specificity being confirmed using both a NO donor [S-nitroso-N-acetyl-penicillamine (SNAP)] and a NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, C-PTIO]. Using 40 lM DAF-2DA, basal levels of intracellular NO were measured which varied in different Leishmania species; addition of conventional anti-leishmanial drugs, antimony and miltefosine translated into a dramatic increase in DAF-2T fluorescence. Furthermore, the assay also measured levels of NO in macrophages, but needed a 20 fold lower concentration of DAF-2DA, being 2 lM. Following parasitization, levels of NO decreased which was normalized following treatment with anti-leishmanial drugs. Similarly monocytes of patients with visceral leishmaniasis at disease presentation showed decreased levels of NO which too reverted on completion of treatment. Taken together, this study opens new perspectives of research regarding monocyte function and provides a real time approach for monitoring the effect of anti-leishmanial compounds. ' International Society for Advancement of Cytometry Key termsanti-leishmanial; DAF-2DA; flow cytometry; leishmaniasis; nitric oxide LEISHMANIA are intracellular protozoan parasites that infect host mononuclear phagocytes, the resultant complex of diseases being leishmaniasis affecting 12 million people world wide in 88 countries (1). This disease is characterized by development of dermal lesions that may be cutaneous leishmaniasis (CL), diffuse cutaneous leishmaniasis (DCL), or mucocutaneous leishmaniasis (MCL) as also there can be systemic involvement as in the case of visceral leishmaniasis (VL), which is potentially fatal if left untreated (2).This obligate intracellular parasite resides and multiplies within macrophages, and therefore it should be able to evade the cytotoxic mechanisms innately operative within the macrophages for its survival (3). One of the predominant cytotoxic mechanisms includes production of reactive nitrogen intermediates, which the Leishmania parasite effectively decreases to ensure its survival (4,5).

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“…It is generally accepted that reactive oxygen species (ROS), including nitric oxide (NO), superoxide, and peroxynitrite, kill intraerythrocytic malarial parasites (5,8,29). The most cited mechanism for parasite killing is that acute Plasmodium infection induces gamma interferon-producing Th1 cells, which in turn activate macrophages to secrete parasiticidal NO and ROS (29,30).…”

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confidence: 99%

Plasmodium bergheiResists Killing by Reactive Oxygen Species

et al. 2005

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Reactive oxygen species (ROS) are widely believed to kill malarial parasites. C57BL/6 mice injected with P. berghei inocula incubated with supraphysiological doses of NO (<150 M) or with peroxynitrite (220 M), however, exhibited parasitemia similar to that seen with those given control inocula, and there was no difference in disease development. Only treatment of inocula with NO doses nearing saturation (>1.2 mM) resulted in no detectable parasitemia in the recipients; flow cytometric analysis with a vital dye (hydroethidine) indicated that 1.5 mM NO lysed the erythrocytes rather than killing the parasites. The hemoglobin level in the inocula was about 8 M; the hemoglobin was mainly oxyhemoglobin (oxyHb) (96%), which was converted to methemoglobin (>95%) after treatment with 150 M NO. The concentrations of 150 M of NO and 220 M of peroxynitrite were far in excess of the hemoglobin concentration (ϳ8 M), and yet no parasite killing was detected. We therefore conclude that hemoglobin protects Plasmodium parasites from ROS, but the parasite likely possesses intrinsic defense mechanisms against ROS.Malaria, a reemerging disease (20) caused by the parasite of the genus Plasmodium, remains refractory to the development of a vaccine in part due to incomplete understanding of the mechanism(s) underlying parasite killing by the immune system. It is generally accepted that reactive oxygen species (ROS), including nitric oxide (NO), superoxide, and peroxynitrite, kill intraerythrocytic malarial parasites (5,8,29). The most cited mechanism for parasite killing is that acute Plasmodium infection induces gamma interferon-producing Th1 cells, which in turn activate macrophages to secrete parasiticidal NO and ROS (29,30).We propose, however, that the blood stage Plasmodium parasite is virtually immune to the cytotoxic effects of NO and ROS as a consequence of hemoglobin (Hb) NO scavenging and ROS suppression within red blood cells (RBCs). The Plasmodium parasite is surrounded by hemoglobin through most of its asexual blood cycle, because it resides within a parasitophorous vacuole inside erythrocytes. Plasmodium falciparum parasites rupture erythrocytes, releasing progeny merozoites, which invade new RBCs after completing their 48-hour blood stage cycle. This extracellular excursion constitutes a brief period in which the parasite is in principle vulnerable to higher ROS concentrations induced by the infection. However, the disruption of the RBC membrane inevitably releases molecular hemoglobin into the circulation, enhancing ROS scavenging; thus, both inside and outside the red cells the parasite is protected from ROS because ROS are scavenged by hemoglobin.Malaria, therefore, is fundamentally different from most infections, because the parasite is surrounded by hemoglobin and can evade the ROS-based protective mechanism as a consequence of ROS quenching by Hb (2), an antioxidant mechanism that has been overlooked. Although Hb's heme group can undergo redox transitions to higher oxidation states and it can auto-oxidize natural...

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Nitric oxide in parasitic infections

Cited by 204 publications

References 90 publications

Nitric oxide monocyte production levels in patients with the hepatosplenic form of Scistosoma mansoni infection who underwent splenectomy, ligature of the left gastric vein and auto implantation of spleen tissue in the major omentum

Nitric oxide monocyte production levels in patients with the hepatosplenic form of Scistosoma mansoni infection who underwent splenectomy, ligature of the left gastric vein and auto implantation of spleen tissue in the major omentum

Monitoring of intracellular nitric oxide in leishmaniasis: Its applicability in patients with visceral leishmaniasis

Plasmodium bergheiResists Killing by Reactive Oxygen Species

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