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. KEY 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 & INFERENCES: 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.
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 diabeticmice 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. KEY 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 DCpatients, 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 & INFERENCES: 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: Madhusudan Grover; Gianrico Farrugia; Matthew S Lurken; Cheryl E Bernard; Maria Simonetta Faussone-Pellegrini; Thomas C Smyrk; Henry P Parkman; Thomas L Abell; William J Snape; William L Hasler; Aynur Ünalp-Arida; Linda Nguyen; Kenneth L Koch; Jorges Calles; Linda Lee; James Tonascia; Frank A Hamilton; Pankaj J Pasricha Journal: Gastroenterology Date: 2011-02-04 Impact factor: 22.682
Authors: Kyoung Moo Choi; Simon J Gibbons; Tien V Nguyen; Gary J Stoltz; Matthew S Lurken; Tamas Ordog; Joseph H Szurszewski; Gianrico Farrugia Journal: Gastroenterology Date: 2008-09-11 Impact factor: 22.682
Authors: S T Eisenman; S J Gibbons; P-J Verhulst; G Cipriani; D Saur; G Farrugia Journal: Neurogastroenterol Motil Date: 2016-10-25 Impact factor: 3.598
Authors: M Grover; C E Bernard; P J Pasricha; H P Parkman; S J Gibbons; J Tonascia; K L Koch; R W McCallum; I Sarosiek; W L Hasler; L A B Nguyen; T L Abell; W J Snape; M L Kendrick; T A Kellogg; T J McKenzie; F A Hamilton; G Farrugia Journal: Neurogastroenterol Motil Date: 2017-01-09 Impact factor: 3.598
Authors: Madhusudan Grover; Surendra Dasari; Cheryl E Bernard; Lakshmikanth L Chikkamenahalli; Katherine P Yates; Pankaj J Pasricha; Irene Sarosiek; Richard McCallum; Kenneth L Koch; Thomas L Abell; Braden Kuo; Robert J Shulman; Simon J Gibbons; Travis J McKenzie; Todd A Kellogg; Michael L Kendrick; James Tonascia; Frank A Hamilton; Henry P Parkman; Gianrico Farrugia Journal: Am J Physiol Gastrointest Liver Physiol Date: 2019-09-04 Impact factor: 4.052