Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction
Lung natural killer cells play a major counter-regulatory role in pulmonary vascular hyperpermeability after myocardial infarction
复制标题
肺自然杀伤细胞在心肌梗死后肺血管通透性过高中发挥重要的反调节作用
DOI：
10.1161/circresaha.114.302625
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发表时间：
2014
期刊：
影响因子：
20.1
通讯作者：
Sano M
中科院分区：
文献类型：
--
作者：
Yan X;Hegab AE;Endo J;Anzai A;Matsuhashi T;Katsumata Y;Ito K;Yamamoto T;Betsuyaku T;Shinmura K;Shen W;Vivier E;Fukuda K;Sano M
NK细胞是天然免疫系统的淋巴细胞，在不同的器官中发挥特异性和小生境特异性的作用。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。方法和结果小鼠NK细胞的耗竭对细胞因子的表达几乎没有影响（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塑。然而，这些小鼠表现出与富含蛋白质、高渗透性肺泡水肿相关的严重呼吸窘迫，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。CD 107 a阳性和干扰素-γ阳性细胞群无变化，而IL-10阳性细胞群增加。将来自野生型小鼠而非IL-10敲除小鼠的NK细胞连续转移到NK细胞耗尽的小鼠中拯救了呼吸表型。IL-1β介导的葡聚糖从肺内皮细胞单层的泄漏也被阻断与NK细胞从野生型小鼠，但不是从IL-10 knockout mice.ConclusionsThis study is the first to identify a critical role for lung NK cells in protecting lung from development of cardiogenic pulmonary edema after myocardial infarction.
RationaleNatural killer (NK) cells are lymphocytes of the innate immune system that play specialized and niche-specific roles in distinct organs.ObjectiveWe investigated the possible function of NK cells in the pathogenesis of congestive heart failure after myocardial infarction.Methods and ResultsDepletion 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.ConclusionsThis 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.