title: Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction.
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 3 days 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 1-3 days post-MI, whereas M2 macrophages represented the predominant macrophage subset after 5 days. 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.
authors: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors: Xiaoxiang
authors: X
authors: Yan
authors: Atsushi
authors: A
authors: Anzai
authors: Yoshinori
authors: Y
authors: Katsumata
authors: Tomohiro
authors: T
authors: Matsuhashi
authors: Kentaro
authors: K
authors: Ito
authors: Jin
authors: J
authors: Endo
authors: Tsunehisa
authors: T
authors: Yamamoto
authors: Akiko
authors: A
authors: Takeshima
authors: Ken
authors: K
authors: Shinmura
authors: Weifeng
authors: W
authors: Shen
authors: Keiichi
authors: K
authors: Fukuda
authors: Motoaki
authors: M
authors: Sano
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D000090062:Kruppel-Like Factor 4; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000276:immunology*
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D017493:Leukocyte Common Antigens
keywords: ASC; DAMPs; DC; Damage-associated molecular patterns; Dendritic cell; Flow cytometry; IR; Immune response; Ischemia–reperfusion; Jmjd3; Jumonji domain containing 3; Klf4; Kruppel-like factor 4; LV; Left ventricular; Macrophage polarity; Myocardial infarction; Pycard; Regulatory T cell; Reperfusion therapy; Treg