title: Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum.
abstract: BACKGROUND
  Animal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of human gastroparesis is unclear. Our aim was to determine changes in macrophages and other cell types in the gastric antrum muscularis propria of patients with diabetic and idiopathic gastroparesis.
  
  
  METHODS
  Full thickness gastric antrum biopsies were obtained from patients enrolled in the Gastroparesis Clinical Research Consortium (11 diabetic, 6 idiopathic) and 5 controls. Immunolabeling and quantitative assessment was done for interstitial cells of Cajal (ICC) (Kit), enteric nerves protein gene product 9.5, neuronal nitric oxide synthase, vasoactive intestinal peptide, substance P, tyrosine hydroxylase), overall immune cells (CD45) and anti-inflammatory macrophages (CD206). Gastric emptying was assessed using nuclear medicine scintigraphy and symptom severity using the Gastroparesis Cardinal Symptom Index.
  
  
  RESULTS
  Both diabetic and idiopathic gastroparesis patients showed loss of ICC as compared to controls (Mean [standard error of mean]/hpf: diabetic, 2.28 [0.16]; idiopathic, 2.53 [0.47]; controls, 6.05 [0.62]; P=.004). Overall immune cell population (CD45) was unchanged but there was a loss of anti-inflammatory macrophages (CD206) in circular muscle (diabetic, 3.87 [0.32]; idiopathic, 4.16 [0.52]; controls, 6.59 [1.09]; P=.04) and myenteric plexus (diabetic, 3.83 [0.27]; idiopathic, 3.59 [0.68]; controls, 7.46 [0.51]; P=.004). There was correlation between the number of ICC and CD206-positive cells (r=.55, P=.008). Enteric nerves (PGP9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04).
  
  
  CONCLUSIONS
  Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Grover
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Bernard
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Pasricha
authors.affiliation: Temple University, Philadelphia, PA, USA.
authors.forename: H P
authors.initials: HP
authors.lastname: Parkman
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Gibbons
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Tonascia
authors.affiliation: Wake Forest University, Winston-Salem, NC, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Koch
authors.affiliation: Texas Tech University, El Paso, TX, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: McCallum
authors.affiliation: Texas Tech University, El Paso, TX, USA.
authors.forename: I
authors.initials: I
authors.lastname: Sarosiek
authors.affiliation: University of Michigan, Ann Arbor, MI, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: Hasler
authors.affiliation: Stanford University, Palo Alto, CA, USA.
authors.forename: L A B
authors.initials: LAB
authors.lastname: Nguyen
authors.affiliation: University of Louisville, Louisville, KY, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Abell
authors.affiliation: California Pacific Medical Center, San Francisco, CA, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Snape
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Kendrick
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Kellogg
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: McKenzie
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Hamilton
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: G
authors.initials: G
authors.lastname: Farrugia
mesh_terms: D000328:Adult; D048909:Diabetes Complications / Q000378:metabolism* / Q000473:pathology; D017615:Enteric Nervous System / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D018589:Gastroparesis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000378:metabolism / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism*; D008875:Middle Aged; D011706:Pyloric Antrum / Q000378:metabolism* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055815:Young Adult
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface
keywords: enteric nervous system; gastrointestinal motility; immune cells; interstitial cells of Cajal; macrophages