Nutritional stimulation of the cholecystokinin-1 receptor (CCK-1R) and acetylcholine receptor (nAChR)-mediated vagal reflex was shown to reduce inflammation and preserve intestinal integrity. Mast cells are important effectors of the innate immune response, therefore modulation of mucosal cells is a potential therapeutic target to control the acute response in the intestine. The present study investigates intestinal responsiveness upon nutritional activation of the vagal anti- during acute inflammation. Mucosal mast cell degranulation was induced mice by administration of Salmonella enterica LPS. Lipid-rich enteral prior to LPS significantly decreased circulatory levels of mouse mast protease at 30 minutes post-LPS compared with isocaloric low-lipid fasting. CCK-1R blockage reversed the inhibitory effects of lipid-rich whereas stimulation of the peripheral CCK-1R mimicked nutritional mast inhibition. The effects of lipid-rich nutrition were negated by nAChR chlorisondamine and alpha-bungarotoxin and vagal intestinal denervation. release of beta-hexosaminidase by MC/9 mast cells following LPS or IgE- complexes was dose-dependently inhibited by acetylcholine and nicotine. Application of GSK1345038A, a specific agonist of the nAChR alpha7, in marrow derived mast cells from nAChR beta2-/- and wild types indicated cholinergic inhibition of mast cells is mediated by the nAChR alpha7 and independent of the nAChR beta2. Together, the current study reveals cells as a previously unknown target of the nutritional anti- reflex.
|Journal||American Journal of Physiology-Gastrointestinal and Liver Physiology|
|Publication status||Published - 1 Jan 2013|
de Haan, J., Hadfoune, M., Lubbers, T., Hodin, C. M. I., Lenaerts, K., Ito, A., Verbaeys, I. Y., Skynner, M. J., Cailotto, C., van der Vliet, J., de Jonge, W. J., Greve, J. W., & Buurman, W. A. (2013). Lipid-rich enteral nutrition regulates mucosal mast cell activation via the vagal anti-inflammatory reflex. American Journal of Physiology-Gastrointestinal and Liver Physiology, 305(5), G383-G391. https://doi.org/10.1152/ajpgi.00333.2012