scholarly journals The Protective Role of Bacillus Anthracis Exosporium in Macrophage-Mediated Killing by Nitric Oxide

2007 ◽  
Author(s):  
John Weaver ◽  
Tae Jin Kang ◽  
Kimberly Raines ◽  
Guan-Liang Cao ◽  
Stephen Hibbs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bacillus Anthracis ◽  
Protective Role ◽  
Oxygen Species ◽  
Activated Macrophages ◽  
Positive Bacterium ◽  
Bacterium Bacillus ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive exposure to antibacterial killing mechanisms by activated macrophages is key to its germination and survival. These antibacterial killing mechanisms include, but are not limited to the generation of free radicals such as nitric oxide (•NO) and superoxide (O2•−) from the upregulation of inducible nitric oxide synthase (NOS 2) along with products derived from them, e.g., peroxynitrite (ONOO−), as part of microbicidal activity. However questions still remain as to how these species are involved in microbial killing, specifically with respect to B. anthracis. In a previous study, we demonstrated that exposure of primary murine macrophages to sonicated B. anthracis endospores up-regulated NOS 2 and demonstrated a •NO-dependent bactericidal response, but unanswered in that study was which of the NOS 2-derived reactive oxygen species was responsible for the observed bactericidal response. Since NOS 2 also generates O2•−, experiments were designed to determine whether NOS 2 formed ONOO− from the reaction of •NO with O2•− and if so, was ONOO− microbicidal toward B. anthracis.

scholarly journals Protective Role of Bacillus anthracis Exosporium in Macrophage-Mediated Killing by Nitric Oxide

2007 ◽  
Vol 75 (8) ◽  
pp. 3894-3901 ◽  
Author(s):  
John Weaver ◽  
Tae Jin Kang ◽  
Kimberly W. Raines ◽  
Guan-Liang Cao ◽  
Stephen Hibbs ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Bacillus Anthracis ◽  
Protective Role ◽  
No Production ◽  
Activated Macrophages ◽  
Macrophage Infection ◽  
Positive Bacterium ◽  
Microbicidal Activity ◽  
Murine Macrophages

ABSTRACT The ability of the endospore-forming, gram-positive bacterium Bacillus anthracis to survive in activated macrophages is key to its germination and survival. In a previous publication, we discovered that exposure of primary murine macrophages to B. anthracis endospores upregulated NOS 2 concomitant with an ·NO-dependent bactericidal response. Since NOS 2 also generates O2·−, experiments were designed to determine whether NOS 2 formed peroxynitrite (ONOO−) from the reaction of ·NO with O2·− and if so, was ONOO− microbicidal toward B. anthracis. Our findings suggest that ONOO− was formed upon macrophage infection by B. anthracis endospores; however, ONOO− does not appear to exhibit microbicidal activity toward this bacterium. In contrast, the exosporium of B. anthracis, which exhibits arginase activity, protected B. anthracis from macrophage-mediated killing by decreasing ·NO levels in the macrophage. Thus, the ability of B. anthracis to subvert ·NO production has important implications in the control of B. anthracis-induced infection.

scholarly journals Nanoparticles Containing Hyaluronan Acid and Astragalus Polysaccharides for Treating Osteoarthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Gongbiao Lu ◽  
Lin Du ◽  
Jishou Lu ◽  
Liuzhong Jin
Keyword(s):  
Nitric Oxide ◽  
Drug Release ◽  
Drug Loading ◽  
Protective Role ◽  
High Drug ◽  
Astragalus Polysaccharides ◽  
Oxide Synthase ◽  
High Drug Loading ◽  
Inducible Nitric Oxide

The pathogeny of osteoarthritis (OA) is very complicated and still is one of the difficulties in a treating procedure. Here, we constructed nanoparticles using hyaluronan acid (HA) and astragalus polysaccharides (APS) for OA therapy. We assessed OA biomarkers and IL-1β-induced matrix metalloproteinase (MMP) expressions. Nanoparticles of 100 nm showed high drug loading of 28.6% (w/w) and extended drug release of 59% over 1 month. Our results demonstrated that nano treatment significantly improved IL-1β-induced cell viability of chondrocytes. Induction of MMP-9, MMP-13, and TNF-α was alleviated by nanoparticles. Furthermore, nano elevated the expression of osteopontin (OPN) and attenuated inducible nitric oxide synthase (iNOS) protein. Our data indicated the protective role of HA and APS-capsuled nanoparticles in OA treatment.

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 Myeloid-Derived Suppressor Cells in Trypanosoma cruzi Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Manuel Fresno ◽  
Núria Gironès
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Trypanosoma Cruzi ◽  
Reactive Oxygen ◽  
Suppressor Cells ◽  
Oxygen Species ◽  
Arginase 1 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Myeloid-derived suppressor cells (MDSCs) are immature heterogeneous myeloid cells that expand in pathologic conditions as cancer, trauma, and infection. Although characterization of MDSCs is continuously revisited, the best feature is their suppressor activity. There are many markers for MDSC identification, it is distinctive that they express inducible nitric oxide synthase (iNOS) and arginase 1, which can mediate immune suppression. MDSCs can have a medullary origin as a result of emergency myelopoiesis, but also can have an extramedullary origin. Early studies on Trypanosoma cruzi infection showed severe immunosuppression, and several mechanisms involving parasite antigens and host cell mediators were described as inhibition of IL-2 and IL-2R. Another mechanism of immunosuppression involving tumor necrosis factor/interferon γ-dependent nitric oxide production by inducible nitric oxide synthase was also described. Moreover, other studies showed that nitric oxide was produced by CD11b+ Gr-1+ MDSCs in the spleen, and later iNOS and arginase 1 expressed in CD11b+Ly6C+Ly6Glo monocytic MDSC were found in spleen and heart of T. cruzi infected mice that suppressed T cell proliferation. Uncontrolled expansion of monocytic MDSCs leads to L-arginine depletion which hinders nitric oxide production leading to death. Supplement of L-arginine partially reverts L-arginine depletion and survival, suggesting that L-arginine could be administered along with anti-parasitical drugs. On the other hand, pharmacological inhibition of MDSCs leads to death in mice, suggesting that some expansion of MDSCs is needed for an efficient immune response. The role of signaling molecules mediating immune suppression as reactive oxygen species, reactive nitrogen species, as well as prostaglandin E2, characteristics of MDSCs, in T. cruzi infection is not fully understood. We review and discuss the role of these reactive species mediators produced by MDSCs. Finally, we discuss the latest results that link the SLAMF1 immune receptor with reactive oxygen species. Interaction of the parasite with the SLAMF1 modulates parasite virulence through myeloid cell infectivity and reactive oxygen species production. We discuss the possible strategies for targeting MDSCs and SLAMF1 receptor in acute Trypanosoma cruzi infection in mice, to evaluate a possible translational application in human acute infections.

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.

Vasculoprotective Role of Inducible Nitric Oxide Synthase at Inflammatory Coronary Lesions Induced by Chronic Treatment With Interleukin-1β in Pigs in Vivo

Circulation ◽  
1997 ◽  
Vol 96 (9) ◽  
pp. 3104-3111 ◽  
Author(s):  
Yoshihiro Fukumoto ◽  
Hiroaki Shimokawa ◽  
Toshiyuki Kozai ◽  
Toshiaki Kadokami ◽  
Kouichi Kuwata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Chronic Treatment ◽  
Interleukin 1Β ◽  
Coronary Lesions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Suppressive effects of sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on the production of NO and ROS in LPS-stimulated RAW264.7 cells

2020 ◽  
Vol 85 (4) ◽  
pp. 882-889
Author(s):  
Yan Liang ◽  
Shijiao Zha ◽  
Masanobu Tentaku ◽  
Takasi Okimura ◽  
Zedong Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ascophyllum Nodosum ◽  
Sulfated Polysaccharide ◽  
Intracellular Reactive Oxygen Species ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Oxide Synthase ◽  
Dose Dependent ◽  
Inducible Nitric Oxide

ABSTRACT In this study, we found that a sulfated polysaccharide isolated from the brown alga Ascophyllum nodosum, ascophyllan, showed suppressive effects on stimulated RAW264.7 cells. Ascophyllan significantly inhibited expression of inducible nitric oxide synthase mRNA and excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner without affecting the viability of RAW264.7 cells. Ascophyllan also reduced the elevated level of intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells. Furthermore, preincubation with ascophyllan resulted in concentration-dependent decrease in ROS production in phorbol 12-myristate-13-acetate-stimulated RAW264.7 cells. Our results suggest that ascophyllan can exhibit anti-inflammatory effects on stimulated macrophages mainly through the attenuation of NO and ROS productions.

Detection of inducible nitric oxide synthase inSchistosoma japonicumandS. mansoni

2004 ◽  
Vol 78 (1) ◽  
pp. 47-50 ◽  
Author(s):  
X.-C. Long ◽  
M. Bahgat ◽  
K. Chlichlia ◽  
A. Ruppel ◽  
Y.-L. Li
Keyword(s):  
Nitric Oxide ◽  
Molecular Weight ◽  
Inducible Nitric Oxide Synthase ◽  
Mouse Liver ◽  
Apparent Molecular Weight ◽  
Western Blots ◽  
Oxide Synthase ◽  
Host Tissues ◽  
Inducible Nitric Oxide

AbstractSchistosoma japonicumandS. mansoniwere tested for reactivity with an anti-inducible nitric oxide (iNOS) antibody and the distribution of iNOS was studied by immunofluorescent tests in different stages of the parasites. Reactivity was associated with the tegument in both larval schistosomes (sporocysts and cercariae) and eggs. With adult worms, the majority of the immunofluorescence was predominantly subtegumental inS. japonicumand parenchymal inS. mansoni. Fluorescence was also observed in host tissues (snails and mouse liver). In Western blots, the enzyme ofS. japonicumhad an apparent molecular weight of about 210 kDa. The possible role of worm and host iNOS in the parasite–host interrelation remains to be clarified.

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