title: Association of low numbers of CD206-positive cells with loss of ICC in the gastric body of patients with diabetic gastroparesis.
abstract: BACKGROUND
  There is increasing evidence for specific cellular changes in the stomach of patients with diabetic (DG) and idiopathic (IG) gastroparesis. The most significant findings are loss of interstitial cells of Cajal (ICC), neuronal abnormalities, and an immune cellular infiltrate. Studies done in diabetic mice have shown a cytoprotective effect of CD206+ M2 macrophages. To quantify overall immune cellular infiltrate, identify macrophage populations, and quantify CD206+ and iNOS+ cells. To investigate associations between cellular phenotypes and ICC.
  
  
  METHODS
  Full thickness gastric body biopsies were obtained from non-diabetic controls (C), diabetic controls (DC), DG, and IG patients. Sections were labeled for CD45, CD206, Kit, iNOS, and putative human macrophage markers (HAM56, CD68, and EMR1). Immunoreactive cells were quantified from the circular muscle layer.
  
  
  RESULTS
  Significantly fewer ICC were detected in DG and IG tissues, but there were no differences in the numbers of cells immunoreactive for other markers between patient groups. There was a significant correlation between the number of CD206+ cells and ICC in DG and DC patients, but not in C and IG and a significant correlation between iNOS+ cells and ICC in the DC group, but not the other groups. CD68 and HAM56 reliably labeled the same cell populations, but EMR1 labeled other cell types.
  
  
  CONCLUSIONS
  Depletion of ICC and correlation with changes in CD206+ cell numbers in DC and DG patients suggests that in humans, like mice, CD206+ macrophages may play a cytoprotective role in diabetes. These findings may lead to novel therapeutic options, targeting alternatively activated macrophages.
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Bernard
authors.forename: S J
authors.initials: SJ
authors.lastname: Gibbons
authors.forename: I S
authors.initials: IS
authors.lastname: Mann
authors.forename: L
authors.initials: L
authors.lastname: Froschauer
authors.forename: H P
authors.initials: HP
authors.lastname: Parkman
authors.forename: S
authors.initials: S
authors.lastname: Harbison
authors.forename: T L
authors.initials: TL
authors.lastname: Abell
authors.forename: W J
authors.initials: WJ
authors.lastname: Snape
authors.forename: W L
authors.initials: WL
authors.lastname: Hasler
authors.forename: R W
authors.initials: RW
authors.lastname: McCallum
authors.forename: I
authors.initials: I
authors.lastname: Sarosiek
authors.forename: L A B
authors.initials: LA
authors.lastname: Nguyen
authors.forename: K L
authors.initials: KL
authors.lastname: Koch
authors.forename: J
authors.initials: J
authors.lastname: Tonascia
authors.forename: F A
authors.initials: FA
authors.lastname: Hamilton
authors.forename: M L
authors.initials: ML
authors.lastname: Kendrick
authors.forename: K R
authors.initials: KR
authors.lastname: Shen
authors.forename: P J
authors.initials: PJ
authors.lastname: Pasricha
authors.forename: G
authors.initials: G
authors.lastname: Farrugia
mesh_terms: D000328:Adult; D002452:Cell Count; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D005260:Female; D018589:Gastroparesis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D006801:Humans; D056885:Interstitial Cells of Cajal / Q000473:pathology*; D037181:Lectins, C-Type; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008875:Middle Aged; D011956:Receptors, Cell Surface; D013270:Stomach / Q000276:immunology / Q000473:pathology*
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface
keywords: gastroparesis; interstitial cells of Cajal; macrophages