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Diabetic and idiopathic gastroparesis is associated with loss of CD 206‐positive macrophages in the gastric antrum
Author(s) -
Grover M.,
Bernard C. E.,
Pasricha P. J.,
Parkman H. P.,
Gibbons S. J.,
Tonascia J.,
Koch K. L.,
McCallum R. W.,
Sarosiek I.,
Hasler W. L.,
Nguyen L. A. B.,
Abell T. L.,
Snape W. J.,
Kendrick M. L.,
Kellogg T. A.,
McKenzie T. J.,
Hamilton F. A.,
Farrugia G.
Publication year - 2017
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.13018
Subject(s) - gastroparesis , medicine , interstitial cell of cajal , gastroenterology , antrum , gastric emptying , pathophysiology , diabetes mellitus , stomach , pathology , immunohistochemistry , endocrinology
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 ( CD 45) and anti‐inflammatory macrophages ( CD 206). 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 ( CD 45) was unchanged but there was a loss of anti‐inflammatory macrophages ( CD 206) 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 CD 206‐positive cells ( r =.55, P =.008). Enteric nerves ( PGP 9.5) were unchanged: diabetic, 33.64 (3.45); idiopathic, 41.26 (6.40); controls, 46.80 (6.04). Conclusion Loss of antral CD 206‐positive anti‐inflammatory macrophages is a key feature in human gastroparesis and it is associates with ICC loss.