From the Department of Cardiology, Rui Jin Hospital, Medical School of Jiaotong University, Shanghai, PR China (X.Y., W.S.); Departments of Cardiology (X.Y., J.E., A.A., T.M., Y.K., K.I., T.Y., K.F., M.S.), Pulmonary Medicine (A.E.H., T.B.), and Geriatric Medicine (K.S.), Keio University School of Medicine, Tokyo, Japan; Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, INSERM, Marseille, France (E.V.); Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Tokyo, Japan (M.S.).
Circ Res. 2014 Feb 14;114(4):637-49. doi: 10.1161/CIRCRESAHA.114.302625. Epub 2013 Dec 23.
Natural killer (NK) cells are lymphocytes of the innate immune system that play specialized and niche-specific roles in distinct organs.
We investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction.
Depletion of NK cells from mice had little effect on cytokine expression (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), neutrophil and macrophage infiltration into infarcted myocardium, or left ventricular remodeling after myocardial infarction. However, these mice exhibited severe respiratory distress associated with protein-rich, high-permeability alveolar edema accompanied by neutrophil infiltration. In addition, there were 20-fold more NK cells in the mouse lungs than in heart, and these cells were accumulated around the vasculature. CD107a-positive and interferon-γ-positive cell populations were unchanged, whereas IL-10-positive populations increased. Adoptive transfer of NK cells from wild-type mice, but not from IL-10 knockout mice, into the NK cell-depleted mice rescued the respiratory phenotype. IL-1β-mediated dextran leakage from a lung endothelial cell monolayer was also blocked by coculture with NK cells from wild-type mice but not from IL-10 knockout mice.
This study is the first to identify a critical role for lung NK cells in protecting lung from the development of cardiogenic pulmonary edema after myocardial infarction.
自然杀伤 (NK) 细胞是先天免疫系统的淋巴细胞，在不同的器官中发挥专门的、特定位置的作用。
我们研究了 NK 细胞在心肌梗死后充血性心力衰竭发病机制中的可能作用。
从小鼠中耗尽 NK 细胞对细胞因子表达（肿瘤坏死因子-α、白细胞介素 [IL]-6 和 IL-1β）、中性粒细胞和巨噬细胞浸润梗死心肌或心肌梗死后左心室重构几乎没有影响。然而，这些小鼠表现出严重的呼吸窘迫，伴有富含蛋白质、高通透性的肺泡水肿，伴有中性粒细胞浸润。此外，小鼠肺部的 NK 细胞比心脏多 20 倍，这些细胞聚集在血管周围。CD107a 阳性和干扰素-γ阳性细胞群没有变化，而 IL-10 阳性细胞群增加。从野生型小鼠而非 IL-10 敲除小鼠中过继转移 NK 细胞到 NK 细胞耗竭小鼠中挽救了呼吸表型。与来自野生型小鼠而非 IL-10 敲除小鼠的 NK 细胞共培养也阻止了白细胞介素-1β介导的肺内皮细胞单层葡聚糖渗漏。
这项研究首次确定了肺 NK 细胞在保护肺免受心肌梗死后心源性肺水肿发展中的关键作用。
