Parasite killing in murine malaria does not require nitric oxide production

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 139-143 ◽  
Author(s):  
N. FAVRE ◽  
B. RYFFEL ◽  
W. RUDIN
Keyword(s):  
Nitric Oxide ◽  
Blood Stage ◽  
No Production ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Stage Parasite ◽  
Blood Stage Malaria ◽  
Inducible Nitric Oxide

Nitric oxide (NO) production has been suggested to play a role as effector molecule in the control of the malarial infections. However, the roles of this molecule are debated. To assess whether blood-stage parasite killing is NO dependent, we investigated the course of blood-stage Plasmodium chabaudi chabaudi (Pcc) infections in inducible nitric oxide synthase (iNOS)-deficient mice. Parasitaemia, haematological alterations, and survival were not affected by the lack of iNOS. To exclude a role of NO produced by other NOS, controls included NO suppression by oral administration of aminoguanidine (AG), a NOS inhibitor. As in iNOS-deficient mice, no difference in the parasitaemia course, survival and haematological values was observed after AG treatment. Our results indicate that NO production is not required for protection against malaria in our murine experimental model. However, C57BL/6 mice treated with AG lost their resistance to Pcc infections, suggesting that the requirement for NO production for parasite killing in murine blood-stage malaria might be strain dependent.

The development of murine cerebral malaria does not require nitric oxide production

Parasitology ◽  
1999 ◽  
Vol 118 (2) ◽  
pp. 135-138 ◽  
Author(s):  
N. FAVRE ◽  
B. RYFFEL ◽  
W. RUDIN
Keyword(s):  
Nitric Oxide ◽  
Cerebral Malaria ◽  
Plasmodium Berghei ◽  
No Production ◽  
Survival And Development ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Inducible Nitric Oxide

Nitric oxide (NO) production has been suggested to be required for the development of cerebral malaria. However, the importance of this molecule for the appearance of this pathology is debated. To assess whether murine cerebral malaria is NO dependent, we investigated the course of blood-stage Plasmodium berghei ANKA (PbA) infections in inducible nitric oxide synthase (iNOS)-deficient mice. Parasitaemia, haematological alterations, survival and development of cerebral malaria were not affected by the lack of iNOS. To exclude a role of NO produced by other NOS, controls included NO suppression by oral administration of aminoguanidine (AG), a NOS inhibitor. As in iNOS-deficient mice, no difference in the parasitaemia course, survival and haematological values was observed after AG treatment. Our results indicate that NO production is not a crucial factor for the development of murine cerebral malaria.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

scholarly journals Inducible nitric oxide synthase provides protection against injury-induced thrombosis in female mice

2011 ◽  
Vol 301 (2) ◽  
pp. H617-H624 ◽  
Author(s):  
Rita K. Upmacis ◽  
Hao Shen ◽  
Lea Esther S. Benguigui ◽  
Brian D. Lamon ◽  
Ruba S. Deeb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ex Vivo ◽  
Physiological Role ◽  
Thrombotic Occlusion ◽  
Female Mice ◽  
Eicosanoid Production ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Inducible Nitric Oxide

Nitric oxide (NO) is an important vasoactive molecule produced by three NO synthase (NOS) enzymes: neuronal (nNOS), inducible (iNOS), and endothelial NOS (eNOS). While eNOS contributes to blood vessel dilation that protects against the development of hypertension, iNOS has been primarily implicated as a disease-promoting isoform during atherogenesis. Despite this, iNOS may play a physiological role via the modulation of cyclooxygenase and thromboregulatory eicosanoid production. Herein, we examined the role of iNOS in a murine model of thrombosis. Blood flow was measured in carotid arteries of male and female wild-type (WT) and iNOS-deficient mice following ferric chloride-induced thrombosis. Female WT mice were more resistant to thrombotic occlusion than male counterparts but became more susceptible upon iNOS deletion. In contrast, male mice (with and without iNOS deletion) were equally susceptible to thrombosis. Deletion of iNOS was not associated with a change in the balance of thromboxane A2 (TxA2) or antithrombotic prostacyclin (PGI2). Compared with male counterparts, female WT mice exhibited increased urinary nitrite and nitrate levels and enhanced ex vivo induction of iNOS in hearts and aortas. Our findings suggest that iNOS-derived NO in female WT mice may attenuate the effects of vascular injury. Thus, although iNOS is detrimental during atherogenesis, physiological iNOS levels may contribute to providing protection against thrombotic occlusion, a phenomenon that may be enhanced in female mice.

scholarly journals Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology

1999 ◽  
Vol 80 (11) ◽  
pp. 2997-3005 ◽  
Author(s):  
C. Bartholdy ◽  
A. Nansen ◽  
J. Erbo Christensen ◽  
O. Marker ◽  
A. Randrup Thomsen
Keyword(s):  
Nitric Oxide ◽  
T Cell ◽  
Lymphocytic Choriomeningitis ◽  
Wild Type ◽  
Cell Mediated Immune Response ◽  
Oxide Synthase ◽  
Deficient Mice ◽  
Lcmv Infection ◽  
Inducible Nitric Oxide

By using mice with a targetted disruption in the gene encoding inducible nitric-oxide synthase (iNOS), we have studied the role of nitric oxide (NO) in lymphocytic choriomeningitis virus (LCMV)-induced, T cell-mediated protective immunity and immunopathology. The afferent phase of the T cell-mediated immune response was found to be unaltered in iNOS-deficient mice compared with wild-type C57BL/6 mice, and LCMV- induced general immunosuppression was equally pronounced in both strains. In vivo analysis revealed identical kinetics of virus clearance, as well as unaltered clinical severity of systemic LCMV infection in both strains. Concerning the outcome of intracerebral infection, no significant differences were found between iNOS-deficient and wild-type mice in the number or composition of mononuclear cells found in the cerebrospinal fluid on day 6 post-infection. Likewise, NO did not influence the up-regulation of proinflammatory cytokine/chemokine genes significantly, nor did it influence the development of fatal meningitis. However, a reduced virus-specific delayed-type hypersensitivity reaction was observed in iNOS-deficient mice compared with both IFN-γ-deficient and wild-type mice. This might suggest a role of NO in regulating vascular reactivity in the context of T cell-mediated inflammation. In conclusion, these findings indicate a minimal role for iNOS/NO in the host response to LCMV. Except for a reduced local oedema in the knockout mice, iNOS/NO seems to be redundant in controlling both the afferent and efferent phases of the T cell-mediated immune response to LCMV infection.

scholarly journals Further evidence for the role of nitric oxide in maternal aggression: effects of L-NAME on maternal aggression towards female intruders in Wistar rats

2009 ◽  
pp. 591-598
Author(s):  
S Ankarali ◽  
HC Ankarali ◽  
C Marangoz
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Aggressive Behavior ◽  
Wistar Rats ◽  
No Production ◽  
Maternal Aggression ◽  
Prairie Voles ◽  
Nos Inhibitor ◽  
Oxide Synthase

It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG -nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms.

scholarly journals Clinical and Serologic Manifestations of Autoimmune Disease in MRL-lpr/lpr Mice Lacking Nitric Oxide Synthase Type 2

1997 ◽  
Vol 186 (3) ◽  
pp. 365-373 ◽  
Author(s):  
Gary S. Gilkeson ◽  
John S. Mudgett ◽  
Michael F. Seldin ◽  
Phil Ruiz ◽  
Audrey A. Alexander ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Immunoblot Analysis ◽  
Peritoneal Macrophages ◽  
No Production ◽  
Renal Vessels ◽  
Dna Antibodies ◽  
Nos Inhibitor ◽  
Oxide Synthase

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL–lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomethyl–arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL–lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL–lpr/lpr mice, mice with targeted disruption of NOS2 were produced by homologous recombination and bred to MRL–lpr/lpr mice to the N4 generation. MRL–lpr/lpr littermates homozygous for disrupted NOS2 (−/−), heterozygous for disrupted NOS2 (+/−), or wildtype (+/+) were derived for this study. Measures of NO production were markedly decreased in the MRL-lpr/lpr (−/−) mice compared with MRL-lpr/lpr (+/+) mice, with intermediate production by the MRL-lpr/lpr (+/−) mice. There was no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney, and peritoneal macrophages of the (−/−) animals, whereas that of (+/+) was high and (+/−) intermediate. The (−/−) mice developed glomerular and synovial pathology similar to that of the (+/−) and (+/+) mice. However, (−/−) mice and (+/−) mice had significantly less vasculitis of medium-sized renal vessels than (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (−/−) mice as compared with (+/+) mice, but levels of anti-DNA antibodies were comparable in all groups. Our findings show that NO derived from NOS2 has a variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting heterogeneity in disease mechanisms.

scholarly journals Novel role of the nitrite transporter NirC in Salmonella pathogenesis: SPI2-dependent suppression of inducible nitric oxide synthase in activated macrophages

Microbiology ◽  
2009 ◽  
Vol 155 (8) ◽  
pp. 2476-2489 ◽  
Author(s):  
Priyanka Das ◽  
Amit Lahiri ◽  
Ayan Lahiri ◽  
Dipshikha Chakravortty
Keyword(s):  
Nitric Oxide ◽  
Type Strain ◽  
Wild Type Strain ◽  
No Production ◽  
Activated Macrophages ◽  
Wild Type ◽  
Raw264.7 Macrophages ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Activation of macrophages by interferon gamma (IFN-γ) and the subsequent production of nitric oxide (NO) are critical for the host defence against Salmonella enterica serovar Typhimurium infection. We report here the inhibition of IFN-γ-induced NO production in RAW264.7 macrophages infected with wild-type Salmonella. This phenomenon was shown to be dependent on the nirC gene, which encodes a potential nitrite transporter. We observed a higher NO output from IFN-γ-treated macrophages infected with a nirC mutant of Salmonella. The nirC mutant also showed significantly decreased intracellular proliferation in a NO-dependent manner in activated RAW264.7 macrophages and in liver, spleen and secondary lymph nodes of mice, which was restored by complementing the gene in trans. Under acidified nitrite stress, a twofold more pronounced NO-mediated repression of SPI2 was observed in the nirC knockout strain compared to the wild-type. This enhanced SPI2 repression in the nirC knockout led to a higher level of STAT-1 phosphorylation and inducible nitric oxide synthase (iNOS) expression than seen with the wild-type strain. In iNOS knockout mice, the organ load of the nirC knockout strain was similar to that of the wild-type strain, indicating that the mutant is exclusively sensitive to the host nitrosative stress. Taken together, these results reveal that intracellular Salmonella evade killing in activated macrophages by downregulating IFN-γ-induced NO production, and they highlight the critical role of nirC as a virulence gene.

scholarly journals Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts

2013 ◽  
Vol 304 (7) ◽  
pp. G673-G679
Author(s):  
Yishi Chen ◽  
Taned Chitapanarux ◽  
Jianfeng Wu ◽  
Russell K. Soon ◽  
Andrew C. Melton ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
No Signaling ◽  
Inflammatory Bowel ◽  
Relaxation Responses ◽  
Oxide Synthase ◽  
Human And Mouse ◽  
Inducible Nitric Oxide

Contraction of intestinal myofibroblasts (IMF) contributes to the development of strictures and fistulas seen in inflammatory bowel disease, but the mechanisms that regulate tension within these cells are poorly understood. In this study we investigated the role of nitric oxide (NO) signaling in C-type natriuretic peptide (CNP)-induced relaxation of IMF. We found that treatment with ODQ, a soluble guanylyl cyclase (sGC) inhibitor, or NG-nitro-l-arginine (l-NNA) or NG-monomethyl-l-arginine (l-NMMA), inhibitors of NO production, all impaired the relaxation of human and mouse IMF in response to CNP. ODQ, l-NNA, and l-NMMA also prevented CNP-induced elevations in cGMP concentrations, and l-NNA or l-NMMA blocked CNP-induced decreases in myosin light phosphorylation. IMF isolated from transgenic mice deficient in inducible nitric oxide synthase (iNOS) had reduced relaxation responses to CNP compared with IMF from control mice and were insensitive to the effects of ODQ, l-NNA, and l-NMMA on CNP treatment. Together these data indicate that stimulation of sGC though NO produced by iNOS activation is required for maximal CNP-induced relaxation in IMF.

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