title: DiabeticCsf1op/opmice lacking macrophages are protected against the development of delayed gastric emptying.
abstract: OBJECTIVE
  Diabetic gastroparesis is associated with changes in interstitial cells of Cajal (ICC), neurons and smooth muscle cells in both animal models and humans. Macrophages appear to be critical to the development of cellular damage that leads to delayed gastric emptying but the mechanisms involved are not well understood.Csf1op/op(Op/Op) mice lack biologically active Csf1, resulting in the absence of Csf1-dependent tissue macrophages. The aim of this study was to useCsf1op/opmice to determine the role of macrophages in the development of delayed gastric emptying.
  
  
  METHODS
  Animals were injected with streptozotocin to make them diabetic. Gastric emptying was determined weekly. Immunohistochemistry was used to identify macrophages and ICC networks in the gastric muscular layers. Oxidative stress was measured by serum malondialdehyde (MDA) levels. Quantitative, reverse transcription PCR was used to measure levels of mRNA.
  
  
  RESULTS
  Csf1op/opmice had normal ICC. With onset of diabetes bothCsf1op/opand wild typeCsf1+/+mice developed increased levels of oxidative stress (75.8 ± 9.1 and 41.2±13.6 nmol/mL MDA respectively). Wild typeCsf1+/+mice developed delayed gastric emptying after onset of diabetes (4/13) whereas no diabeticCsf1op/opmouse developed delayed gastric emptying (0/15, P=0.035). ICC were disrupted in diabetic wild typeCsf1+/+mice with delayed gastric emptying but remained normal in diabeticCsf1op/opmice.
  
  
  CONCLUSIONS
  Cellular injury and development of delayed gastric emptying in diabetes requires the presence of muscle layer macrophages. Targeting macrophages may be an effective therapeutic option to prevent cellular damage and development of delayed gastric emptying in diabetes.
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Cipriani
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Gibbons
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Verhulst
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Kyoung Moo
authors.initials: KM
authors.lastname: Choi
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Seth T
authors.initials: ST
authors.lastname: Eisenman
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Hein
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Ordog
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Linden
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Szurszewski
authors.affiliation: Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, MN, 55905, USA.
authors.forename: Gianrico
authors.initials: G
authors.lastname: Farrugia
keywords: Gastroparesis; diabetic complications; interstitial cells of Cajal