O34 – The Enteric Nervous System (ENS) Neuropeptide, Bombesin (BBS), Maintains Goblet Cell Function During Parenteral Nutrition (PN)
Author(s):
Background: Parenteral Nutrition (PN) increases the risk of infection in critically ill patients. Recently, we identified a PN-induced decrease in GI tract innate mucosal immunity during PN which included lower production & secretion of the goblet cell protein, MUC2. MUC2 coats the mucosa concentrating defensive molecules made by the mucosal immune systems. The goblet cells produce and secrete other peptides as well, including trefoil factor 3 (TFF3). TFF3 is implicated in protection and repair of the mucosa & its release is governed by neuropeptides produced by the ENS. Experimentally, BBS, a gastrin-releasing neuropeptide analogue, reverses PN-induced defects in gut and respiratory acquired immunity.
Hypothesis: Since PN reduces goblet cell function, we hypothesized that the ENS neuropeptide BBS would increase production & secretion of goblet cell products.
Methods: 2 days after IV cannulation, randomized male ICR mice received Chow (n=7), PN (n=6), or PN+BBS (15 ug TID) (n=7) for 5 days. Small intestine wash fluid (SIWF) was collected for analysis of the goblet cell products MUC2 and TFF3 by western blot. Defined segments of ileum were analyzed for tissue MUC2.
Results: Compared to chow, PN significantly reduced levels of MUC2 (Chow: 34543 + 6535 vs PN: 8232 + 762, p < 0.05) and TFF3 (Chow: 16909 + 1334 vs PN: 5814 + 1030, p < 0.05) in small intestinal fluid samples. Addition of BBS to PN significantly increased intestinal fluid levels of MUC2 (PN: 8232 + 762 vs PN+BBS: 21020 + 2226, p < 0.05) and TFF3 (PN: 5814 + 1030 vs PN+BBS: 16996 + 2957, p < 0.05) compared to PN alone and back to Chow levels. There were no differences in tissue MUC2 levels between Chow and PN mice (Chow: 77425 + 5107 vs PN: 77190 + 2674, p > 0.05). However, PN+BBS significantly increased MUC2 tissue levels compared to chow and PN (PN+BBS: 94189 + 5374 vs Chow: 77425 + 5107).
Conclusions: PN significantly impairs the goblet cell component of innate mucosal immune function. The ENS neuropeptide, bombesin, significantly improves this innate immune dysfunction and establishes the link between ENS and goblet cell function.