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.
Highlights
Myocarditis is a major cause of heart failure in young adults
To investigate the role of lymphocyte function-associated antigen 1 (LFA-1) for cardiac inflammation in myocarditis, we evaluated leukocyte infiltration and the heart weight/body weight ratio in the experimental autoimmune myocarditis (EAM) model after blocking LFA-1
Leukocyte infiltration into the inflamed cardiac tissue, which was analyzed histologically using a semi-quantitative score, was significantly increased at day 21 in immunized mice without antibody treatment (PBS) or with isotype control antibody treatment compared to sham-immunized mice, as expected
Summary
Myocarditis is a major cause of heart failure in young adults. Sustained cardiac inflammation may eventually lead to cardiac remodeling and end-stage heart failure with dilation of the ventricles and deteriorating contractility of the cardiac muscle, a condition called inflammatory dilated cardiomyopathy (DCMi) [1]. We recently showed that neutrophils play a critical role for cardiac inflammation in the experimental autoimmune myocarditis (EAM) mouse model which resembles the immunological and histopathological features of post-viral heart disease [2,3]. In this model, cardiac inflammation was induced by administration of a cardiac peptide together
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