1. Academic Validation
  2. Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis

Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis

  • Cells. 2019 Oct 17;8(10):1267. doi: 10.3390/cells8101267.
Ludwig T Weckbach 1 2 3 4 Andreas Uhl 5 6 7 Felicitas Boehm 8 9 10 Valentina Seitelberger 11 Bruno C Huber 12 Gabriela Kania 13 Stefan Brunner 14 Ulrich Grabmaier 15 16
Affiliations

Affiliations

  • 1 Medizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, Germany. [email protected].
  • 2 Walter Brendel Centre of Experimental Medicine, University Hospital, LMU Munich, 82152 Planegg-Martinsried, Germany. [email protected].
  • 3 Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, LMU Munich, 82152 Planegg-Martinsried, Germany. [email protected].
  • 4 German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, 80802 Munich, Germany. [email protected].
  • 5 Medizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, Germany. [email protected].
  • 6 Walter Brendel Centre of Experimental Medicine, University Hospital, LMU Munich, 82152 Planegg-Martinsried, Germany. [email protected].
  • 7 Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, LMU Munich, 82152 Planegg-Martinsried, Germany. [email protected].
  • 8 Medizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, Germany. [email protected].
  • 9 Walter Brendel Centre of Experimental Medicine, University Hospital, LMU Munich, 82152 Planegg-Martinsried, Germany. [email protected].
  • 10 Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, LMU Munich, 82152 Planegg-Martinsried, Germany. [email protected].
  • 11 Medizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, Germany. [email protected].
  • 12 Medizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, Germany. [email protected].
  • 13 Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, 8952 Schlieren, Switzerland. [email protected].
  • 14 Medizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, Germany. [email protected].
  • 15 Medizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, Germany. [email protected].
  • 16 German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, 80802 Munich, Germany. [email protected].
Abstract

The lymphocyte function-associated antigen 1 (LFA-1) is a member of the beta2-integrin family and plays a pivotal role for T cell activation and leukocyte trafficking under inflammatory conditions. Blocking LFA-1 has reduced or aggravated inflammation depending on the inflammation model. To investigate the effect of LFA-1 in myocarditis, mice with experimental autoimmune myocarditis (EAM) were treated with a function blocking anti-LFA-1 antibody from day 1 of disease until day 21, the peak of inflammation. Cardiac inflammation was evaluated by measuring infiltration of leukocytes into the inflamed cardiac tissue using histology and flow cytometry and was assessed by analysis of the heart weight/body weight ratio. LFA-1 antibody treatment severely enhanced leukocyte infiltration, in particular infiltration of CD11b+ monocytes, F4/80+ macrophages, CD4+ T cells, Ly6G+ neutrophils, and CD133+ progenitor cells at peak of inflammation which was accompanied by an increased heart weight/body weight ratio. Thus, blocking LFA-1 starting at the time of immunization severely aggravated acute cardiac inflammation in the EAM model.

Keywords

inflammation; leukocytes; myocarditis.

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