Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Nat Commun. 2020 Dec 16;11(1):6396. doi: 10.1038/s41467-020-19297-5.
Clinical studies reveal changes in blood eosinophil counts and eosinophil cationic proteins that may serve as risk factors for human coronary heart diseases. Here we report an increase of blood or heart eosinophil counts in humans and mice after myocardial infarction (MI), mostly in the infarct region. Genetic or inducible depletion of eosinophils exacerbates cardiac dysfunction, cell death, and fibrosis post-MI, with concurrent acute increase of heart and chronic increase of splenic neutrophils and monocytes. Mechanistic studies reveal roles of eosinophil IL4 and cationic protein mEar1 in blocking HO- and hypoxia-induced mouse and human cardiomyocyte death, TGF-β-induced cardiac fibroblast Smad2/3 activation, and TNF-α-induced neutrophil adhesion on the heart endothelial cell monolayer. In vitro-cultured eosinophils from WT mice or recombinant mEar1 protein, but not eosinophils from IL4-deficient mice, effectively correct exacerbated cardiac dysfunctions in eosinophil-deficient ∆dblGATA mice. This study establishes a cardioprotective role of eosinophils in post-MI hearts.
临床研究显示，血液嗜酸性粒细胞计数和嗜酸性粒细胞阳离子蛋白的变化可能是人类冠心病的危险因素。在这里，我们报告了心肌梗死后（MI）人类和小鼠血液或心脏嗜酸性粒细胞计数的增加，主要在梗死区域。嗜酸性粒细胞的遗传或诱导性耗竭会加剧 MI 后的心脏功能障碍、细胞死亡和纤维化，同时伴有心脏的急性增加和脾脏中性粒细胞和单核细胞的慢性增加。机制研究表明，嗜酸性粒细胞 IL4 和阳离子蛋白 mEar1 在阻断 HO-和缺氧诱导的小鼠和人类心肌细胞死亡、TGF-β诱导的心肌成纤维细胞 Smad2/3 激活以及 TNF-α诱导的中性粒细胞黏附在心脏内皮细胞单层上发挥作用。来自 WT 小鼠或重组 mEar1 蛋白的体外培养嗜酸性粒细胞，但不是来自 IL4 缺陷型小鼠的嗜酸性粒细胞，可有效纠正嗜酸性粒细胞缺陷 ∆dblGATA 小鼠中加剧的心脏功能障碍。这项研究确立了嗜酸性粒细胞在 MI 后心脏中的心脏保护作用。
