Expression of Nitric Oxide Synthase in a Murine Model of Viral Myocarditis Induced by Coxsackievirus B3

Mikami, S; Kawashima, Seinosuke; Kanazawa, Kenji; Hirata, Ken Ichi; Katayama, Yuko; Hotta, Haku; Hayashi, Yoshitake; Itô, Hiroshi; Yokoyama, Mitsuhiro

doi:10.1006/bbrc.1996.0519

Cited by 63 publications

(33 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Immunohistochemical analysis of MN-11 tumors demonstrated iNOS in infiltrating neutrophils and biochemical measurements of tissue extracts showed NOS activity. The presence of iNOS in mouse neutrophils 52,53 and the presence of high NOS activity in some human cancers has been reported. 54 Further evidence of the presence of RNS in MN-11 tumors was provided by immunohistochemical analysis for nitrotyrosine; immunoreactivity was observed throughout the tumor, both in the cytoplasm and the nucleus of tumor cells.…”

Section: Discussionmentioning

confidence: 94%

Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Sandhu

Privora

Wenckebach

et al. 2000

The American Journal of Pathology

View full text Add to dashboard Cite

Mutatect MN-11 is a tumor line that can be grown subcutaneously in syngeneic C57BL/6 mice. The frequency of spontaneously arising mutants at the hypoxanthine phosphoribosyltransferase (Hprt) locus was observed to be elevated as a result of in vivo growth. The objective of the present study was to identify factors in the tumor microenvironment that might explain this increase in mutant frequency (MF). When tumors were examined histologically, neutrophils were found to be the predominant infiltrating cell type. Quantitative estimates of the number of neutrophils and MF of tumors in different animals revealed a statistically significant correlation (r ‫؍‬ 0.63, P < 0.0001). Immunohistochemical analysis for inducible nitric oxide synthase (iNOS) demonstrated its presence, mainly in neutrophils. Biochemical analysis of tumor homogenates for nitric oxide synthase (NOS) activity indicated a statistically significant correlation with MF (r ‫؍‬ 0.77, P < 0.0001). Nitrotyrosine was detected throughout the tumor immunohistochemically; both cytoplasmic and nuclear staining was seen. To increase the number of infiltrating neutrophils, tumors were injected with chemoattractant interleukin-8 and prostaglandin E2. This produced a statistically significant increase in neutrophil content (P ‫؍‬ 0.005) and MF (P ‫؍‬ 0.0002). As in control MN-11 tumors, neutrophil content and MF were strongly correlated (r ‫؍‬ 0.63, P ‫؍‬ 0.003). Because neutrophils are a potential source of genotoxic reactive oxygen and/or nitrogen species, our results support the notion that these tumor-infiltrating cells may be mutagenic and contribute to the burden of genetic abnormalities associated with tumor progression.

show abstract

Section: Discussionmentioning

confidence: 94%

Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Sandhu

Privora

Wenckebach

et al. 2000

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…For example, murine myocardial cells produce NO in vitro via the induction of NOS by cytokines such as IFN-␥ and interleukin (IL)-1␤ 10 or by IL-6 and TNF-␣ in the presence of lipopolysaccharide. 11 Furthermore, iNOS has been shown to be inducible in the myocardium of animals infected with coxsackievirus 12 or with T cruzi 13 and in mice with experimental autoimmune myocarditis. 14 The ability of NO to mediate microbicidal activity against a wide variety of parasites, 15 including T cruzi, 4,5,9 the observation that myocytes produce NO in response to TNF-␣ and IL-1␤, 10,11 and the fact that these cytokines are detected in the heart of T cruzi-infected rats 13 prompted us to investigate whether cardiac myocytes could be involved in NO-dependent trypanocidal activity.…”

mentioning

confidence: 99%

Trypanosoma cruzi –Infected Cardiomyocytes Produce Chemokines and Cytokines That Trigger Potent Nitric Oxide–Dependent Trypanocidal Activity

Machado¹,

Martins²,

Aliberti³

et al. 2000

Circulation

228

216

View full text Add to dashboard Cite

Background-The pathogenesis of myocarditis that occurs in Trypanosoma cruzi-infected mice is still poorly understood.Therefore, it is important to know the mediators that trigger leukocyte migration to the heart as well as the cellular source of these possible mediators. In this study, we investigated (1) NO synthase (NOS) induction, (2) NO synthesis, (3) trypanocidal activity, and (4) chemokine and cytokine mRNA expression by isolated cardiomyocytes infected with T cruzi. Methods and Results-Mouse cardiomyocytes were isolated, infected with T cruzi, and evaluated for induction of inducible NOS (iNOS), nitrite production, trypanocidal activity, and cytokine and chemokine mRNA expression. We found that T cruzi-infected murine embryonic cardiomyocytes produced nitrite and expressed mRNAs for the chemokines chemokine growth-related oncogene, monokine induced by interferon-␥, macrophage inflammatory protein-2, interferon-␥-inducible protein, RANTES, and monocyte chemotactic protein, for iNOS, and for the cytokines tumor necrosis factor (TNF)-␣ and interleukin (IL)-1␤. Separate addition of IL-1␤, interferon-␥, TNF-␣ or monocyte chemotactic protein, macrophage inflammatory protein-2, and interferon-␥-inducible protein, to cultured cardiomyocytes resulted in NO production but low trypanocidal activity. However, simultaneous addition of IL-1␤, interferon-␥, and TNF-␣ or the chemokines to cultures resulted in the induction of iNOS, high levels of nitrite, and a marked trypanocidal activity. The iNOS/L-arginine pathway mediated the latter activity, inasmuch as it was inhibited by treatment with N G -monomethyl-L-arginine. Conclusions-These results indicate that iNOS activation and the proinflammatory cytokines and chemokines produced by cardiomyocytes are likely to control parasite growth and cell influx, thus contributing to the pathogenesis of chagasic cardiomyopathy seen in T cruzi-infected mice. (Circulation. 2000;102:3003-3008.)

show abstract

“…Additionally, inducible nitric oxide (NO) synthase (iNOS) induced by activated macrophages acts to encourage NO to eliminate infected viruses. It has been reported that excessive release of NO strongly damages myocardial cells (Mikami et al, 1996). Infiltration by inflammatory cells, including T cells and natural killer cells, peaks 7-14 days after viral infection and causes widespread necrosis of myocardial cells (Seko et al, 1993).…”

Section: Development and Strategy For Treatment During The Acute Phasementioning

confidence: 99%

Acute Myocarditis in Emergency Medicine

Ikegami¹,

Tase²

2011

Myocarditis

View full text Add to dashboard Cite

Expression of Nitric Oxide Synthase in a Murine Model of Viral Myocarditis Induced by Coxsackievirus B3

Cited by 63 publications

References 0 publications

Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Neutrophils, Nitric Oxide Synthase, and Mutations in the Mutatect Murine Tumor Model

Trypanosoma cruzi –Infected Cardiomyocytes Produce Chemokines and Cytokines That Trigger Potent Nitric Oxide–Dependent Trypanocidal Activity

Acute Myocarditis in Emergency Medicine

Contact Info

Product

Resources

About