Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex
Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex
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DOI：
10.1152/ajpgi.00333.2012
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发表时间：
2013-09-01
影响因子：
4.5
通讯作者：
Buurman, Wim A.
中科院分区：
文献类型：
--
作者：
de Haan, Jacco J.;Hadfoune, M'hamed;Buurman, Wim A.
胆囊收缩素-1 受体 (CCK-1R) 和烟碱乙酰胆碱受体 (nAChR) 介导的迷走神经反射的营养刺激被证明可以减少炎症并保持肠道完整性。肥大细胞是先天免疫反应的重要早期效应器；因此，调节粘膜肥大细胞是控制肠道急性炎症反应的潜在治疗靶点。本研究探讨了急性炎症期间迷走神经抗炎反射的营养激活作用下肠道肥大细胞的反应性。通过给予肠沙门氏菌 LPS，在 C57/Bl6 小鼠中诱导粘膜肥大细胞脱粒。与等热量低脂营养或禁食相比，LPS 前富含脂质的肠内喂养显着降低了 LPS 后 30 分钟小鼠肥大细胞蛋白酶的循环水平。 CCK-1R 阻断逆转了富含脂质喂养的抑制作用，而刺激外周 CCK-1R 则模拟了营养性肥大细胞抑制。富含脂质的营养的作用被 nAChR 阻滞剂氯磺丹明和 α-金环蛇毒素以及迷走肠去神经支配所抵消。因此，LPS或IgE-卵清蛋白复合物后MC/9肥大细胞释放β-己糖胺酶受到乙酰胆碱和尼古丁的剂量依赖性抑制。 GSK1345038A（nAChR α(7) 的特异性激动剂）在来自 nAChR β(2)-/- 和野生型的骨髓源性肥大细胞中的应用表明，肥大细胞的胆碱能抑制是由 nAChR α(7) 介导的，并且独立于 nAChR β(2)。总之，本研究揭示粘膜肥大细胞是以前未知的营养抗炎迷走神经反射的目标。
Nutritional stimulation of the cholecystokinin-1 receptor (CCK-1R) and nicotinic acetylcholine receptor (nAChR)-mediated vagal reflex was shown to reduce inflammation and preserve intestinal integrity. Mast cells are important early effectors of the innate immune response; therefore modulation of mucosal mast cells is a potential therapeutic target to control the acute inflammatory response in the intestine. The present study investigates intestinal mast cell responsiveness upon nutritional activation of the vagal anti-inflammatory reflex during acute inflammation. Mucosal mast cell degranulation was induced in C57/Bl6 mice by administration of Salmonella enterica LPS. Lipid-rich enteral feeding prior to LPS significantly decreased circulatory levels of mouse mast cell protease at 30 min post-LPS compared with isocaloric low-lipid nutrition or fasting. CCK-1R blockage reversed the inhibitory effects of lipid-rich feeding, whereas stimulation of the peripheral CCK-1R mimicked nutritional mast cell inhibition. The effects of lipid-rich nutrition were negated by nAChR blockers chlorisondamine and alpha-bungarotoxin and vagal intestinal denervation. Accordingly, release of beta-hexosaminidase by MC/9 mast cells following LPS or IgE-ovalbumin complexes was dose dependently inhibited by acetylcholine and nicotine. Application of GSK1345038A, a specific agonist of the nAChR alpha(7), in bone marrow-derived mast cells from nAChR beta(2)-/- and wild types indicated that cholinergic inhibition of mast cells is mediated by the nAChR alpha(7) and is independent of the nAChR beta(2). Together, the present study reveals mucosal mast cells as a previously unknown target of the nutritional anti-inflammatory vagal reflex.