Mast Cells Play a Critical Role in the Pathogenesis of Viral Myocarditis

Higuchi, Hiroyoshi; Hara, Masatake; Yamamoto, Keita; Miyamoto, Tadashi; Kinoshita, Makoto; Yamada, Toshiaki; Uchiyama, Köji; Matsumori, Akira

doi:10.1161/circulationaha.107.741595

Cited by 58 publications

(47 citation statements)

References 45 publications

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“…53 Mast cells in the heart rapidly degranulate after CVB3 infection. 54 Moreover, mast cell-deficient mice are protected against encephalomyocarditis viral myocarditis, 55 which is a similar phenotype to PAR2ko mice. We are currently studying the role of mast cells and tryptase in CVB3-induced myocarditis.…”

Section: Mackman 15mentioning

confidence: 95%

Multiple roles of the coagulation protease cascade during virus infection

Antoniak

Mackman

2014

Blood

194

205

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The coagulation cascade is activated during viral infections. This response may be part of the host defense system to limit spread of the pathogen. However, excessive activation of the coagulation cascade can be deleterious. In fact, inhibition of the tissue factor/factor VIIa complex reduced mortality in a monkey model of Ebola hemorrhagic fever. Other studies showed that incorporation of tissue factor into the envelope of herpes simplex virus increases infection of endothelial cells and mice. Furthermore, binding of factor X to adenovirus serotype 5 enhances infection of hepatocytes but also increases the activation of the innate immune response to the virus. Coagulation proteases activate protease-activated receptors (PARs). Interestingly, we and others found that PAR1 and PAR2 modulate the immune response to viral infection. For instance, PAR1 positively regulates TLR3-dependent expression of the antiviral protein interferon β, whereas PAR2 negatively regulates expression during coxsackievirus group B infection. These studies indicate that the coagulation cascade plays multiple roles during viral infections.

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Section: Mackman 15mentioning

confidence: 95%

Multiple roles of the coagulation protease cascade during virus infection

Antoniak

Mackman

2014

Blood

194

205

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“…Recent studies have implicated mast cells in inflammation and tissue remodeling (11,12). Indeed, mast cells reside in many tissues including the heart (13) and participate in the inflammatory process underlying several cardiovascular disorders, such as atherosclerosis (14,15), aortic aneurysm (16,17), heart failure (18), viral myocarditis (19), and ventricular arrhythmia during ischemia/reperfusion injury (20). In particular, mast cell-derived IL-6 and IFN-γ have been reported to promote atherosclerosis and abdominal aortic aneurysm (15,16).…”

Section: Introductionmentioning

confidence: 99%

Cardiac mast cells cause atrial fibrillation through PDGF-A–mediated fibrosis in pressure-overloaded mouse hearts

Liao¹,

Akazawa²,

Tamagawa³

et al. 2010

J. Clin. Invest.

167

130

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Atrial fibrillation (AF) is a common arrhythmia that increases the risk of stroke and heart failure. Here, we have shown that mast cells, key mediators of allergic and immune responses, are critically involved in AF pathogenesis in stressed mouse hearts. Pressure overload induced mast cell infiltration and fibrosis in the atrium and enhanced AF susceptibility following atrial burst stimulation. Both atrial fibrosis and AF inducibility were attenuated by stabilization of mast cells with cromolyn and by BM reconstitution from mast celldeficient WBB6F1-Kit W/W-v mice. When cocultured with cardiac myocytes or fibroblasts, BM-derived mouse mast cells increased platelet-derived growth factor A (PDGF-A) synthesis and promoted cell proliferation and collagen expression in cardiac fibroblasts. These changes were abolished by treatment with a neutralizing antibody specific for PDGF α-receptor (PDGFR-α). Consistent with these data, upregulation of atrial Pdgfa expression in pressure-overloaded hearts was suppressed by BM reconstitution from WBB6F1-Kit W/W-v mice. Furthermore, injection of the neutralizing PDGFR-α-specific antibody attenuated atrial fibrosis and AF inducibility in pressure-overloaded hearts, whereas administration of homodimer of PDGF-A (PDGF-AA) promoted atrial fibrosis and enhanced AF susceptibility in normal hearts. Our results suggest a crucial role for mast cells in AF and highlight a potential application of controlling the mast cell/PDGF-A axis to achieve upstream prevention of AF in stressed hearts.

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“…125 In addition, the few in vivo studies that have examined a role for MCs in protection from viral infection, including infection with (QFHSKDORP\RFDUGLWLV 9LUXV DQG &R[VDFNLH % 9LUXV KDYH VXJJHVWHG WKDW 0& GH¿FLHQF\ results in reduced pathology of the disease. 126,127 However, reconstitution of Wsh mice with MCs restores the pathogenic effects of the viral illness. 126,127 In calves infected with RSV, MC activation and systemic release of their products appears to correlate with the severity of symptoms.…”

Section: Khvh Gdwd Frq¿uphg Iru Wkh ¿Uvw Wlph Wkdw 0andv Duh Dq Lpsruwmentioning

confidence: 99%

“…126,127 However, reconstitution of Wsh mice with MCs restores the pathogenic effects of the viral illness. 126,127 In calves infected with RSV, MC activation and systemic release of their products appears to correlate with the severity of symptoms. [128][129] Finally, in models where large doses of TLR ligands are R DGPLQLVWHUHG WR PLFH 0& GH¿FLHQF\ DSSHDUV WR DPHOLRUDWH WKH SDWKRJHQLF LQÀDPPDWLRQ LQGXFHG E\ WKHVH 7/5 OLJDQGV )RU LQVWDQFH 0& GH¿FLHQF\ UHGXFHG /36LQGXFHG XYHLWLV or cystitis and SM360320 (a TLR7 agonist) induced hypothermia.…”

Section: Khvh Gdwd Frq¿uphg Iru Wkh ¿Uvw Wlph Wkdw 0andv Duh Dq Lpsruwmentioning

confidence: 99%

The Mast Cell in Innate and Adaptive Immunity

Shelburne

Abraham

2011

Mast Cell Biology

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Mast cells (MCs) were once considered only as effector cells in pathogenic IgE- and IgG-mediated responses such as allergy. However, developments over the last 15 years have suggested that MCs have evolved in vertebrates as beneficial effector cells that are involved in the very first inflammatory responses generated during infection. This pro-inflammatory environment has been demonstrated to be important for initiating innate responses in many different models of infection and more recently, in the development of adaptive immunity as well. Interestingly this latter finding has led to the discovery that small MC-activating compounds can behave as adjuvants in vaccine formulations. Thus, our continued understanding of the MC in the context of infectious disease is likely to not only expand our scope of the MC in the normal processes of immunity, but provide new therapeutic targets to combat disease.

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Mast Cells Play a Critical Role in the Pathogenesis of Viral Myocarditis

Cited by 58 publications

References 45 publications

Multiple roles of the coagulation protease cascade during virus infection

Multiple roles of the coagulation protease cascade during virus infection

Cardiac mast cells cause atrial fibrillation through PDGF-A–mediated fibrosis in pressure-overloaded mouse hearts

The Mast Cell in Innate and Adaptive Immunity

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