Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis

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 investig...

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Main Authors: Ludwig T. Weckbach, Andreas Uhl, Felicitas Boehm, Valentina Seitelberger, Bruno C. Huber, Gabriela Kania, Stefan Brunner, Ulrich Grabmaier
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/10/1267
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author Ludwig T. Weckbach
Andreas Uhl
Felicitas Boehm
Valentina Seitelberger
Bruno C. Huber
Gabriela Kania
Stefan Brunner
Ulrich Grabmaier
author_facet Ludwig T. Weckbach
Andreas Uhl
Felicitas Boehm
Valentina Seitelberger
Bruno C. Huber
Gabriela Kania
Stefan Brunner
Ulrich Grabmaier
author_sort Ludwig T. Weckbach
collection DOAJ
description 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.
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spelling doaj.art-e5f28757c2d042a7b1f77924ade788572023-08-02T02:57:37ZengMDPI AGCells2073-44092019-10-01810126710.3390/cells8101267cells8101267Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune MyocarditisLudwig T. Weckbach0Andreas Uhl1Felicitas Boehm2Valentina Seitelberger3Bruno C. Huber4Gabriela Kania5Stefan Brunner6Ulrich Grabmaier7Medizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, GermanyCenter of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, 8952 Schlieren, SwitzerlandMedizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Klinikum der Universität, LMU Munich, 81377 Munich, GermanyThe 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.https://www.mdpi.com/2073-4409/8/10/1267myocarditisinflammationleukocytes
spellingShingle Ludwig T. Weckbach
Andreas Uhl
Felicitas Boehm
Valentina Seitelberger
Bruno C. Huber
Gabriela Kania
Stefan Brunner
Ulrich Grabmaier
Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis
Cells
myocarditis
inflammation
leukocytes
title Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis
title_full Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis
title_fullStr Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis
title_full_unstemmed Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis
title_short Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis
title_sort blocking lfa 1 aggravates cardiac inflammation in experimental autoimmune myocarditis
topic myocarditis
inflammation
leukocytes
url https://www.mdpi.com/2073-4409/8/10/1267
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