Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction

Xiaoxiang Yan, Atsushi Anzai, Yoshinori Katsumata, Tomohiro Matsuhashi, Kentaro Ito, Jin Endo, Tsunehisa Yamamoto, Akiko Takeshima, Ken Shinmura, Weifeng Shen, Keiichi Fukuda, Motoaki Sano

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

Acute myocardial infarction (MI) causes sterile inflammation, which is characterized by recruitment and activation of innate and adaptive immune system cells. Here we delineate the temporal dynamics of immune cell accumulation following MI by flow cytometry. Neutrophils increased immediately to a peak at 3days post-MI. Macrophages were numerically the predominant cells infiltrating the infarcted myocardium, increasing in number over the first week post-MI. Macrophages are functionally heterogeneous, whereby the first responders exhibit high expression levels of proinflammatory mediators, while the late responders express high levels of the anti-inflammatory cytokine IL-10; these macrophages can be classified into M1 and M2 macrophages, respectively, based on surface-marker expression. M1 macrophages dominated at 1-3days post-MI, whereas M2 macrophages represented the predominant macrophage subset after 5days. The M2 macrophages expressed high levels of reparative genes in addition to proinflammatory genes to the same levels as in M1 macrophages. The predominant subset of dendritic cells (DCs) was myeloid DC, which peaked in number on day 7. Th1 and regulatory T cells were the predominant subsets of CD4+ T cells, whereas Th2 and Th17 cells were minor populations. CD8+ T cells, γδT cells, B cells, natural killer (NK) cells and NKT cells peaked on day 7 post-MI. Timely reperfusion reduced the total number of leukocytes accumulated in the post-MI period, shifting the peak of innate immune response towards earlier and blunting the wave of adaptive immune response. In conclusion, these results provide important knowledge necessary for developing successful immunomodulatory therapies.

Original languageEnglish
Pages (from-to)24-35
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume62
DOIs
Publication statusPublished - 2013 Sep 1

Keywords

  • Flow cytometry
  • Immune response
  • Macrophage polarity
  • Myocardial infarction
  • Reperfusion therapy

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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