M Grover1, C E Bernard1, P J Pasricha2, H P Parkman3, S J Gibbons1, J Tonascia4, K L Koch5, R W McCallum6, I Sarosiek6, W L Hasler7, L A B Nguyen8, T L Abell9, W J Snape10, M L Kendrick1, T A Kellogg1, T J McKenzie1, F A Hamilton11, G Farrugia1. 1. Enteric NeuroScience Program, Mayo Clinic, Rochester, MN, USA. 2. Johns Hopkins School of Medicine, Baltimore, MD, USA. 3. Temple University, Philadelphia, PA, USA. 4. Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA. 5. Wake Forest University, Winston-Salem, NC, USA. 6. Texas Tech University, El Paso, TX, USA. 7. University of Michigan, Ann Arbor, MI, USA. 8. Stanford University, Palo Alto, CA, USA. 9. University of Louisville, Louisville, KY, USA. 10. California Pacific Medical Center, San Francisco, CA, USA. 11. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
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). CONCLUSION: Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.
BACKGROUND: Animal studies have increasingly highlighted the role of macrophages in the development of delayed gastric emptying. However, their role in the pathophysiology of humangastroparesis 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 gastroparesispatients 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). CONCLUSION: Loss of antral CD206-positive anti-inflammatory macrophages is a key feature in humangastroparesis and it is associates with ICC loss.
Authors: C E Bernard; S J Gibbons; I S Mann; L Froschauer; H P Parkman; S Harbison; T L Abell; W J Snape; W L Hasler; R W McCallum; I Sarosiek; L A B Nguyen; K L Koch; J Tonascia; F A Hamilton; M L Kendrick; K R Shen; P J Pasricha; G Farrugia Journal: Neurogastroenterol Motil Date: 2014-07-13 Impact factor: 3.598
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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