Mononuclear cell secretome protects from experimental autoimmune myocarditis.
- Hoetzenecker K Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Währinger Gürtel 18-20, 1090 Vienna, Austria.
- Zimmermann M Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Währinger Gürtel 18-20, 1090 Vienna, Austria.
- Hoetzenecker W Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, MA, USA.
- Schweiger T Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Währinger Gürtel 18-20, 1090 Vienna, Austria.
- Kollmann D Institute of Pathophysiology, Medical University Vienna, Vienna, Austria.
- Mildner M Department of Dermatology, Medical University Vienna, Vienna, Austria.
- Hegedus B Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria.
- Mitterbauer A Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Währinger Gürtel 18-20, 1090 Vienna, Austria.
- Hacker S Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Währinger Gürtel 18-20, 1090 Vienna, Austria Department of Plastic and Reconstructive Surgery Medical University of Vienna, Vienna, Austria.
- Birner P Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
- Gabriel C Red Cross Transfusion Service for Upper Austria, Linz, Austria.
- Gyöngyösi M Department of Cardiology, Medical University Vienna, Vienna, Austria.
- Blyszczuk P Division of Cardioimmunology, Cardiovascular Research and Zurich Center for Integrative Human Physiology, Institute of Physiology, University of Zurich, Zurich, Switzerland Department of Medicine, GZO, Zurich Regional Health Center, Wetzikon, Switzerland.
- Eriksson U Division of Cardioimmunology, Cardiovascular Research and Zurich Center for Integrative Human Physiology, Institute of Physiology, University of Zurich, Zurich, Switzerland Department of Medicine, GZO, Zurich Regional Health Center, Wetzikon, Switzerland.
- Ankersmit HJ Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Währinger Gürtel 18-20, 1090 Vienna, Austria hendrik.ankersmit@meduniwien.ac.at.
- 2013-01-17
Published in:
- European heart journal. - 2015
Conditioned medium
Mononuclear cells
Myocarditis
Secretome
Animals
Antibodies
Apoptosis
Autoantibodies
Autoimmune Diseases
CD4-CD8 Ratio
CD4-Positive T-Lymphocytes
CD40 Ligand
CD8-Positive T-Lymphocytes
Caspase Inhibitors
Cell Proliferation
Cells, Cultured
Cytokines
Dendritic Cells
Disease Models, Animal
Fas Ligand Protein
Humans
Mice, Inbred BALB C
Myocarditis
Myosin Heavy Chains
Receptors, TNF-Related Apoptosis-Inducing Ligand
Spleen
English
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.
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.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/eurheartj/ehs459
- PMID 23321350
- Persistent URL
- https://folia.unifr.ch/global/documents/203906
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