Monoclonal antibody therapy for prevention of acute coxsackievirus B3 myocarditis in mice.

Kishimoto, Chiharu; Abelmann, Walter H.

doi:10.1161/01.cir.79.6.1300

Cited by 23 publications

(9 citation statements)

References 26 publications

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“…the induction of apoptosis in T cells, which would otherwise invade the myocardium and cause cardiac damage or potentially transfer viral particles into the heart, could contribute to the cardioprotective effects of CAPs in inflammatory cardiomyopathy. This hypothesis is supported by the findings that splenectomy improves the myocardial infarction outcome [44] and that the use of an antibody against T cells reduces the cardiac damage in myocarditis [31]. Furthermore, we suggest that CAPs are able to exert beneficial effects via the release of paracrine factors, such as IL-10 in an analagous manner to MSCs, which are also trapped in the lungs after i.v.…”

Section: Discussionsupporting

confidence: 67%

“…Since viral progeny release requires apoptosis of infected cells [34], we suggest that the CAPs-mediated reduction in cardiomyocyte apoptosis underlies the decrease in viral progeny release in HL-1 cells and contributes to the decrease in viral load in CVB3-infected mice. Since T cells play an important role in the severity of cardiac damage in CVB3-induced myocarditis [31], we speculate that the observed decrease in cardiac apoptosis and subsequent viral load in CVB3+CAPs mice versus CVB3+PBS mice is due not only to the direct anti-apoptotic effects of CAPs, but also to their immunomodulatory features.…”

Section: Discussionmentioning

confidence: 91%

“…Given the importance of immune cells in the severity and development of myocarditis [31], we analyzed whether and how CAPs have immunomodulatory effects. In vivo , CAPs application reduced the CVB3-induced proliferation/activity of cardiac MNCs in murine acute CVB3-induced myocarditis by 2.9–fold (p<0.05) ( Figure 6A ) and was associated with less cardiac damage ( Figure 6B ).…”

Section: Resultsmentioning

confidence: 99%

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Human Cardiac-Derived Adherent Proliferating Cells Reduce Murine Acute Coxsackievirus B3-Induced Myocarditis

et al. 2011

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BackgroundUnder conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. We recently isolated and identified novel cardiac-derived cells from human cardiac biopsies: cardiac-derived adherent proliferating cells (CAPs). They have similarities with mesenchymal stromal cells, which are known for their anti-apoptotic and immunomodulatory properties. We explored whether CAPs application could be a novel strategy to improve acute Coxsackievirus B3 (CVB3)-induced myocarditis.Methodology/Principal FindingsTo evaluate the safety of our approach, we first analyzed the expression of the coxsackie- and adenovirus receptor (CAR) and the co-receptor CD55 on CAPs, which are both required for effective CVB3 infectivity. We could demonstrate that CAPs only minimally express both receptors, which translates to minimal CVB3 copy numbers, and without viral particle release after CVB3 infection. Co-culture of CAPs with CVB3-infected HL-1 cardiomyocytes resulted in a reduction of CVB3-induced HL-1 apoptosis and viral progeny release. In addition, CAPs reduced CD4 and CD8 T cell proliferation. All CAPs-mediated protective effects were nitric oxide- and interleukin-10-dependent and required interferon-γ. In an acute murine model of CVB3-induced myocarditis, application of CAPs led to a decrease of cardiac apoptosis, cardiac CVB3 viral load and improved left ventricular contractility parameters. This was associated with a decline in cardiac mononuclear cell activity, an increase in T regulatory cells and T cell apoptosis, and an increase in left ventricular interleukin-10 and interferon-γ mRNA expression.ConclusionsWe conclude that CAPs are a unique type of cardiac-derived cells and promising tools to improve acute CVB3-induced myocarditis.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

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Human Cardiac-Derived Adherent Proliferating Cells Reduce Murine Acute Coxsackievirus B3-Induced Myocarditis

et al. 2011

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“…With the spleen being a reservoir of monocytes, which are recruited to the inflammatory heart [178], we suggest that these MSC/CardAPs-mediated immunomodulatory effects in the spleen contributed to the cardioprotective effects of MSCs/CardAPs in inflammatory cardiomyopathy. This hypothesis is supported by the findings that (i) splenectomy improves the myocardial infarction outcome [179], (ii) the use of an antibody against T cells reduces the cardiac damage in myocarditis [180], and (iii) our recent observation that splenocytes isolated from CVB3-infected mice injected with MSCs induce less collagen production in fibroblasts compared to splenocytes from CVB3 mice [127]. …”

Section: Route Of Applicationmentioning

confidence: 79%

Immunomodulatory Effects of Mesenchymal Stromal Cells Revisited in the Context of Inflammatory Cardiomyopathy

Miteva

Linthout

Volk

et al. 2013

Stem Cells International

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Myocarditis is a common inflammatory cardiomyopathy, associated with cardiomyocyte apoptosis, which can lead to chronic left ventricular dysfunction. Under conventional heart failure therapy, inflammatory cardiomyopathy typically has a progressive course, indicating a need for alternative therapeutic strategies to improve long-term outcomes. Experimental and clinical studies consistently support the application of cellular transplantation as a strategy to improve myocardial function. Mesenchymal stromal cells (MSCs) mediate distinct paracrine effects supporting endogenous regeneration, but most important are their remarkable immunoregulatory properties. In this review, an overview of current knowledge on immunopathology in myocarditis will be given. Furthermore, current research regarding the immunomodulatory properties of MSCs in the context of myocarditis will be discussed. Finally, the impact of MSC priming by the environment on their functionality and the advantages of systemic administration of MSCs under myocarditis are outlined.

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“…However, the immune response against CVB3 may be a double-edged sword. For example, depletion of abT cells from CVB3-infected mice leads to a marked reduction in myocardial damage, despite comparable virus titers to control animals (Kishimoto and Abelmann, 1989). Likewise, gdT cells may contribute to immunopathological damage of cardiomyocytes (Huber, 2000;Huber et al, 2001).…”

Section: Acute Cvb3-induced Myocarditismentioning

confidence: 99%

Immunopathological Basis of Virus‐induced Myocarditis

Maier

Krebs

Ludewig

2004

Journal of Immunology Research

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Heart diseases are an important cause of morbidity and mortality in industrialized countries. Dilated cardiomyopathy (DCM), one of the most common heart diseases, may be the consequence of infectionassociated myocardits. Coxsackievirus B3 (CVB3) can be frequently detected in the inflamed heart muscle. CVB3-induced acute myocarditis is most likely the consequence of direct virus-induced myocyte damage, whereas chronic CVB3 infection-associated heart disease is dominated by its immunopathological sequelae. Bona fide autoimmunity, for example, directed against cardiac myosin, may favor chronic destructive immune damage in the heart muscle and thereby promote the development of DCM. The immunopathogenesis of myocarditis and subsequent DCM induced either by pathogens or autoantigens can be investigated in well-established animal models. In this article, we review recent studies on the role of viruses, with particular emphasis on CVB3, and different immunological effector mechanisms in initiation and progression of myocarditis.

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Monoclonal antibody therapy for prevention of acute coxsackievirus B3 myocarditis in mice.

Cited by 23 publications

References 26 publications

Human Cardiac-Derived Adherent Proliferating Cells Reduce Murine Acute Coxsackievirus B3-Induced Myocarditis

Human Cardiac-Derived Adherent Proliferating Cells Reduce Murine Acute Coxsackievirus B3-Induced Myocarditis

Immunomodulatory Effects of Mesenchymal Stromal Cells Revisited in the Context of Inflammatory Cardiomyopathy

Immunopathological Basis of Virus‐induced Myocarditis

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