title: The enteric nervous system neuropeptide, bombesin, reverses innate immune impairments during parenteral nutrition.
abstract: BACKGROUND
  Lack of enteral stimulation during parenteral nutrition (PN) impairs mucosal immunity. Bombesin (BBS), a gastrin-releasing peptide analogue, reverses PN-induced defects in acquired immunity. Paneth cells produce antimicrobial peptides (AMPs) of innate immunity for release after cholinergic stimulation.
  
  
  OBJECTIVE
  Determine if BBS restores AMPs and bactericidal function during PN.
  
  
  METHODS
  Intravenously cannulated male ICR mice were randomized to Chow, PN, or PN+BBS (15 μg 3 times daily, n = 7 per group) for 5 days. Ileum was analyzed for AMPs (Protein: sPLA2 by fluorescence, lysozyme and RegIII-γ by western andcryptdin-4 by ELISA; mRNA: all by RT-PCR). Cholinergic stimulated (100 μM bethanechol) ileal specimens assessed Pseudomonas bactericidal activity. Ileum (Chow: n = 7; PN: n = 9; PN+BBS: n = 8) was assessed for Escherichia coli invasion in ex-vivo culture.
  
  
  RESULTS
  PN significantly decreased most AMPs versus Chow while BBS maintained Chow levels (sPLA2: Chow: 107 + 14*, PN: 44.6 + 7.2, PN+BBS: 78.7 + 13.4* Fl/min/μL/total protein; Lysozyme: Chow: 63.9 + 11.9*, PN: 26.8 + 6.2; PN+BBS: 64.9 + 13.8* lysozyme/total protein; RegIII-γ: Chow: 51.5 + 10.0*, PN: 20.4 + 4.3, PN+BBS: 31.0 + 8.4 RegIII-γ/total protein; Cryptdin-4: Chow: 18.4 + 1.5*, PN: 12.7 + 1.6, PN+BBS: 26.1 + 2.4*† pg/mg [all *P < 0.05 vs PN and †P < 0.05 vs Chow]). Functionally, BBS prevented PN loss of bactericidal activity after cholinergic stimulation (Chow: 25.3 + 3.6*, PN: 13.0 + 3.2; PN+BBS: 27.0 + 4.7* percent bacterial killing, *P < 0.05 vs PN). BBS reduced bacterial invasion in unstimulated tissue barely missing significance (P = 0.06).
  
  
  CONCLUSIONS
  The enteric nervous system (ENS) controls AMP levels in Paneth cells during PN but mucosal protection by innate immunity requires both ENS and parasympathetic stimulation.
authors.affiliation: *Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison †Department of Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China; and ‡Veterans Administration Surgical Services, William S. Middleton Memorial Veterans Hospital, Madison, WI.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Busch
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Heneghan
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Pierre
authors.forename: Xinying
authors.initials: X
authors.lastname: Wang
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kudsk
mesh_terms: D000818:Animals; D001839:Bombesin / Q000008:administration & dosage*; D007082:Ileum / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects* / Q000502:physiology; D018928:Immunity, Mucosal / Q000187:drug effects; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008813:Mice, Inbred ICR; D009113:Muramidase / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000008:administration & dosage*; D000073718:Pancreatitis-Associated Proteins; D019879:Paneth Cells / Q000378:metabolism*; D010288:Parenteral Nutrition; D054497:Phospholipases A2, Secretory / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D023084:alpha-Defensins / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; C490255:Reg3g protein, mouse; D023084:alpha-Defensins; C401847:cryptdin 4, mouse; D054497:Phospholipases A2, Secretory; D009113:Muramidase; D001839:Bombesin