Depletion of NK cells attenuates paraquat-induced acute lung injury by manipulating macrophage polarization
Depletion of NK cells attenuates paraquat-induced acute lung injury by manipulating macrophage polarization
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NK 细胞的耗竭通过控制巨噬细胞极化减轻百草枯诱导的急性肺损伤
DOI：
10.1016/j.intimp.2020.106698
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发表时间：
2020-09-01
影响因子：
5.6
通讯作者：
Peng, Ai
中科院分区：
文献类型：
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作者：
Wu, Mingyu;Zhou, Chunyu;Peng, Ai
急性肺损伤是导致百草枯(PQ)死亡的主要原因。先天免疫系统触发的有害炎症级联反应在PQ诱导的急性肺损伤中起重要作用。然而，自然杀伤(NK)细胞在PQ诱导的急性肺损伤中的作用仍很不清楚，NK细胞是先天反应所必需的。在这里，我们发现在急性PQ中毒模型中，NK细胞的耗竭通过抑制巨噬细胞向M1型的极化来减轻PQ引起的肺损伤。具体地说，在急性PQ中毒的小鼠模型中，肺、脾和外周血中NK细胞的百分比减少。NK细胞被异常激活，表现为激活标志CD69、CD107a和NKG2D上调，抑制标志KLRG1下调。此外，与对照组相比，小鼠NK特异性耗竭显著延长了小鼠的存活时间，改善了PQ治疗后由活性氧引起的损伤。重要的是，NK细胞耗尽减轻了肺内巨噬细胞和中性粒细胞的浸润，并逆转了PQ诱导的巨噬细胞向促炎M1型的极化。我们的研究表明，NK细胞和NK细胞与巨噬细胞的相互作用在PQ诱导的急性肺损伤中起着至关重要的作用。
Acute lung injury is the main causative factor in paraquat dichloride (PQ)-induced mortality. The innate immune system-triggered detrimental inflammatory cascade plays a vital role in PQ-induced acute lung injury. However, the role of natural killer (NK) cells, which are essential for innate response, in PQ-induced acute lung injury remains largely unknown. Here, we found that in an acute PQ poisoning model, depletion of NK cells attenuated PQ-induced lung injury by inhibiting macrophage polarization towards the M1 type. Specifically, the percentages of NK cells were reduced in the lung, spleen, and peripheral blood in a murine model of acute PQ poisoning. NK cells were aberrantly activated, evidenced by upregulation of the activating markers CD69, CD107a, and NKG2D and downregulation of the inhibitive marker KLRG1. Further, NK-specific depletion in mice greatly prolonged the survival time and ameliorated reactive oxygen species-induced damage following PQ treatment compared with the control group. Importantly, NK cell depletion alleviated macrophage and neutrophil infiltration in the lung and reversed PQ induced-macrophage polarization towards the pro-inflammatory M1 type. Our study demonstrates a crucial role of NK cells and NK cell-to-macrophage interaction in PQ-induced acute lung injury.