Mononuclear cell secretome protects from experimental autoimmune myocarditis

Konrad Hoetzenecker, Matthias Zimmermann, Wolfram Hoetzenecker, Thomas Schweiger, Dagmar Kollmann, Michael Mildner, B. Hegedűs, Andreas Mitterbauer, Stefan Hacker, Peter Birner, Christian Gabriel, Mariann Gyöngyösi, Przemyslaw Blyszczuk, Urs Eriksson, Hendrik Jan Ankersmit

Research output: Contribution to journalArticle

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Abstract

Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases.

Original languageEnglish
Pages (from-to)676-685a
JournalEuropean Heart Journal
Volume36
Issue number11
DOIs
Publication statusPublished - Mar 14 2015

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Myocarditis
T-Lymphocytes
Dilated Cardiomyopathy
Inflammation
Cell Survival
Ventricular Myosins
Freund's Adjuvant
Myosin Heavy Chains
Caspase 8
Autoantibodies
Myocardial Ischemia
Cultured Cells
Heart Diseases
Immunization
Anti-Inflammatory Agents
Animal Models
Heart Failure
Apoptosis
Peptides
Serum

Keywords

  • Conditioned medium
  • Mononuclear cells
  • Myocarditis
  • Secretome

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hoetzenecker, K., Zimmermann, M., Hoetzenecker, W., Schweiger, T., Kollmann, D., Mildner, M., ... Ankersmit, H. J. (2015). Mononuclear cell secretome protects from experimental autoimmune myocarditis. European Heart Journal, 36(11), 676-685a. https://doi.org/10.1093/eurheartj/ehs459

Mononuclear cell secretome protects from experimental autoimmune myocarditis. / Hoetzenecker, Konrad; Zimmermann, Matthias; Hoetzenecker, Wolfram; Schweiger, Thomas; Kollmann, Dagmar; Mildner, Michael; Hegedűs, B.; Mitterbauer, Andreas; Hacker, Stefan; Birner, Peter; Gabriel, Christian; Gyöngyösi, Mariann; Blyszczuk, Przemyslaw; Eriksson, Urs; Ankersmit, Hendrik Jan.

In: European Heart Journal, Vol. 36, No. 11, 14.03.2015, p. 676-685a.

Research output: Contribution to journalArticle

Hoetzenecker, K, Zimmermann, M, Hoetzenecker, W, Schweiger, T, Kollmann, D, Mildner, M, Hegedűs, B, Mitterbauer, A, Hacker, S, Birner, P, Gabriel, C, Gyöngyösi, M, Blyszczuk, P, Eriksson, U & Ankersmit, HJ 2015, 'Mononuclear cell secretome protects from experimental autoimmune myocarditis', European Heart Journal, vol. 36, no. 11, pp. 676-685a. https://doi.org/10.1093/eurheartj/ehs459
Hoetzenecker K, Zimmermann M, Hoetzenecker W, Schweiger T, Kollmann D, Mildner M et al. Mononuclear cell secretome protects from experimental autoimmune myocarditis. European Heart Journal. 2015 Mar 14;36(11):676-685a. https://doi.org/10.1093/eurheartj/ehs459
Hoetzenecker, Konrad ; Zimmermann, Matthias ; Hoetzenecker, Wolfram ; Schweiger, Thomas ; Kollmann, Dagmar ; Mildner, Michael ; Hegedűs, B. ; Mitterbauer, Andreas ; Hacker, Stefan ; Birner, Peter ; Gabriel, Christian ; Gyöngyösi, Mariann ; Blyszczuk, Przemyslaw ; Eriksson, Urs ; Ankersmit, Hendrik Jan. / Mononuclear cell secretome protects from experimental autoimmune myocarditis. In: European Heart Journal. 2015 ; Vol. 36, No. 11. pp. 676-685a.
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abstract = "Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases.",
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AU - Zimmermann, Matthias

AU - Hoetzenecker, Wolfram

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AU - Kollmann, Dagmar

AU - Mildner, Michael

AU - Hegedűs, B.

AU - Mitterbauer, Andreas

AU - Hacker, Stefan

AU - Birner, Peter

AU - Gabriel, Christian

AU - Gyöngyösi, Mariann

AU - Blyszczuk, Przemyslaw

AU - Eriksson, Urs

AU - Ankersmit, Hendrik Jan

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N2 - Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases.

AB - Aims Supernatants of serum-free cultured mononuclear cells (MNC) contain a mix of immunomodulating factors (secretome), which have been shown to attenuate detrimental inflammatory responses following myocardial ischaemia. Inflammatory dilated cardiomyopathy (iDCM) is a common cause of heart failure in young patients. Experimental autoimmune myocarditis (EAM) is a CD4+ T cell-dependent model, which mirrors important pathogenic aspects of iDCM. The aim of this study was to determine the influence of MNC secretome on myocardial inflammation in the EAM model. Methods and results BALB/c mice were immunized twice with an alpha myosin heavy chain peptide together with Complete Freund adjuvant. Supernatants from mouse mononuclear cells were collected, dialysed, and injected i.p. at Day 0, Day 7, or Day 14, respectively. Myocarditis severity, T cell responses, and autoantibody formation were assessed at Day 21. The impact of MNC secretome on CD4+ T cell function and viability was evaluated using in vitro proliferation and cell viability assays. A single high-dose application of MNC secretome, injected at Day 14 after the first immunization, effectively attenuated myocardial inflammation. Mechanistically, MNC secretome induced caspase-8-dependent apoptosis in autoreactive CD4+ T cells. Conclusion MNC secretome abrogated myocardial inflammation in a CD4+ T cell-dependent animal model of autoimmune myocarditis. This anti-inflammatory effect of MNC secretome suggests a novel and simple potential treatment concept for inflammatory heart diseases.

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