Natural killer T cell ligand alpha-galactosylceramide protects against gut ischemia reperfusion-induced organ injury in mice
Natural killer T cell ligand alpha-galactosylceramide protects against gut ischemia reperfusion-induced organ injury in mice
复制标题
自然杀伤 T 细胞配体 α-半乳糖神经酰胺可防止小鼠肠道缺血再灌注引起的器官损伤
DOI：
10.1016/j.cyto.2018.08.032
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发表时间：
2018
期刊：
影响因子：
3.8
通讯作者：
Wu Rongqian
中科院分区：
文献类型：
--
作者：
Zhang Jia;Bi Jianbin;Ren Yifan;Du Zhaoqing;Li Teng;Li Qingshan;Ke Mengyun;Dong Jian;Lv Yi;Wu Rongqian
背景与目的缺血再灌注(I/R)损伤是一种危及生命的损伤。免疫反应在I/R所致器官损伤中起重要作用。α-半乳糖神经酰胺(α-GalCer)是一种有效的自然杀伤T细胞刺激物。α-GalCer激活NKT细胞已被证明可以减轻I/R引起的肝脏和心脏损伤。然而，α-GalCer对肠I/R所致器官损伤是否具有保护作用尚不清楚。本研究的目的是验证α-GalCer通过调节免疫反应减轻肠道I/R引起的局部和远程器官损伤的假说。方法在雄性成年小鼠肠系膜上动脉上放置微血管夹30 ，诱导肠缺血。取下夹子后，给予α-GalCer(2 微克/只)或含有0.5%吐温20的生理盐水(载体)。再灌流4 h后采集血、肠、肺和肠系膜淋巴结标本，检测细菌移位、紧密连接蛋白、组织损伤、水肿、细胞凋亡、IL-4、IL-10、干扰素-γ和肿瘤坏死因子-α水平。结果α-GalCer可显著减少肠道I/R后细菌移位至肠、肺和肠系膜淋巴结，恢复紧密连接蛋白，减轻肠和肺损伤。α-GalCer显著刺激IL-4、IL-10和γ的产生，但对α的产生无明显影响。预先给予抗CD1d、IL-4或IL-10抗体，但不用干扰素-γ阻断抗体，可阻断α-GalCer对肠I/R的保护作用。结论α-GalCer可改善肠I/R后肠屏障功能，减轻肠和肺损伤，α-GalCer对肠I/R的保护作用依赖于NKT细胞，并通过上调IL-4和IL-10介导。因此，α-GalCer激活NKT细胞可能成为治疗肠I/R损伤的一种新选择。
Background & AimsGut ischemia reperfusion (I/R) injury is a life-threatening condition. The immune response plays an important role in I/R-induced organ injury. Alpha-galactosylceramide (α-GalCer) is a potent natural killer T (NKT) cell stimulator. Activation of NKT cells by α-GalCer has been shown to reduce I/R-induced injury in the liver and heart. However, whether α-GalCer has any protective effects on gut I/R-induced organ injury remained unknown. The aim of this study was to test the hypothesis that α-GalCer attenuates gut I/R-induced local and remote organ injury through modulating immune responses.MethodsGut ischemia was induced by placing a microvascular clip across the superior mesenteric artery for 30 min in male adult mice. After removing the clip, α-GalCer (2 µg/mouse) or normal saline containing 0.5% Tween 20 (Vehicle) was administered intraperitoneally. Blood, gut, lung and mesenteric lymph node (MLN) samples were collected 4 h after reperfusion to detect bacterial translocation, tight junction protein, tissue damage, edema, apoptosis, IL-4, IL-10, IFN-γ and TNF-α levels.Resultsα-GalCer significantly reduced bacterial translocation to the MLN, restored tight junction protein and attenuated gut and lung injury after gut I/R. α-GalCer markedly stimulated the production of IL-4, IL-10 and IFN-γ, but had no obvious effects on TNF-α production in gut I/R mice. Pretreatment with anti-CD1d, IL-4 or IL-10, but not IFN-γ blocking antibodies abolished the protective effects of α-GalCer in gut I/R.Conclusionsα-GalCer treatment improved gut barrier function and attenuated gut and lung injury after gut I/R. The beneficial effects of α-GalCer in gut I/R were NKT cell dependent and mediated through upregulation of IL-4 and IL-10. Thus, activation of NKT cells by α-GalCer may serve as a novel option in the treatment of gut I/R injury.