title: Mononuclear cell secretome protects from experimental autoimmune myocarditis.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Konrad
authors: K
authors: Hoetzenecker
authors: 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.
authors: Matthias
authors: M
authors: Zimmermann
authors: Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, MA, USA.
authors: Wolfram
authors: W
authors: Hoetzenecker
authors: 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.
authors: Thomas
authors: T
authors: Schweiger
authors: Institute of Pathophysiology, Medical University Vienna, Vienna, Austria.
authors: Dagmar
authors: D
authors: Kollmann
authors: Department of Dermatology, Medical University Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Mildner
authors: Department of Thoracic Surgery, Medical University Vienna, Vienna, Austria.
authors: Balazs
authors: B
authors: Hegedus
authors: 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.
authors: Andreas
authors: A
authors: Mitterbauer
authors: 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.
authors: Stefan
authors: S
authors: Hacker
authors: Clinical Institute of Pathology, Medical University of Vienna, Vienna, Austria.
authors: Peter
authors: P
authors: Birner
authors: Red Cross Transfusion Service for Upper Austria, Linz, Austria.
authors: Christian
authors: C
authors: Gabriel
authors: Department of Cardiology, Medical University Vienna, Vienna, Austria.
authors: Mariann
authors: M
authors: Gyöngyösi
authors: 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.
authors: Przemyslaw
authors: P
authors: Blyszczuk
authors: 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.
authors: Urs
authors: U
authors: Eriksson
authors: 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.
authors: Hendrik Jan
authors: HJ
authors: Ankersmit
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D001323:Autoantibodies / Q000378:metabolism; D001327:Autoimmune Diseases / Q000517:prevention & control*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D023201:CD40 Ligand / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D061945:Caspase Inhibitors / Q000494:pharmacology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000502:physiology; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000276:immunology; D006801:Humans; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000517:prevention & control*; D018995:Myosin Heavy Chains / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000276:immunology; D013154:Spleen / Q000166:cytology
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D061945:Caspase Inhibitors; D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; C584019:Myh6 protein, mouse; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D023201:CD40 Ligand; D018995:Myosin Heavy Chains
keywords: Conditioned medium; Mononuclear cells; Myocarditis; Secretome