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. 2017 Jun;29(6):10.1111/nmo.13018.
doi: 10.1111/nmo.13018. Epub 2017 Jan 9.

Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum

M Grover  1 , C E Bernard  1 , P J Pasricha  2 , H P Parkman  3 , S J Gibbons  1 , J Tonascia  4 , K L Koch  5 , R W McCallum  6 , I Sarosiek  6 , W L Hasler  7 , L A B Nguyen  8 , T L Abell  9 , W J Snape  10 , M L Kendrick  1 , T A Kellogg  1 , T J McKenzie  1 , F A Hamilton  11 , G Farrugia  1 ; NIDDK Gastroparesis Clinical Research Consortium (GpCRC)
Affiliations

Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum

M Grover et al. Neurogastroenterol Motil. 2017 Jun.

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.

Keywords: enteric nervous system; gastrointestinal motility; immune cells; interstitial cells of Cajal; macrophages.

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Conflict of interest statement

Conflicts of interest: No conflicts of interest exist

Figures

Figure 1
Figure 1
c-Kit immunoreactivity (circular muscle) in control (a), diabetic gastroparesis, Db Gp (b) and idiopathic gastroparesis, Id Gp (c) showing significant ICC loss in both diabetic and idiopathic gastroparesis. Arrowhead represents an ICC and arrow represents a mast cell in the field.
Figure 2
Figure 2
CD206 ir (circular muscle) in control (a), diabetic gastroparesis, Db Gp (b) and idiopathic gastroparesis, Id Gp (c); CD206 ir (myenteric plexus) in control (d), diabetic gastroparesis (e) and idiopathic gastroparesis (e), both demonstrating loss of M2 (anti-inflammatory) macrophages (represented by arrowheads) in diabetic and idiopathic gastroparesis.
Figure 3
Figure 3
Correlation of ICC (circular muscle) and CD206 ir cells (circular muscle) showing significant correlation between ICC loss and loss of anti-inflammatory macrophages.
See this image and copyright information in PMC

References

    1. Grover M, Farrugia G, Lurken MS, Bernard CE, Faussone-Pellegrini MS, Smyrk TC, Parkman HP, Abell TL, et al. Cellular changes in diabetic and idiopathic gastroparesis. Gastroenterology. 2011;140:1575 e8–1585 e8. - PMC - PubMed
    1. Faussone-Pellegrini MS, Grover M, Pasricha PJ, Bernard CE, Lurken MS, Smyrk TC, Parkman HP, Abell TL, et al. Ultrastructural differences between diabetic and idiopathic gastroparesis. J Cell Mol Med. 2012;16:1573–1581. - PMC - PubMed
    1. Battaglia E, Bassotti G, Bellone G, Dughera L, Serra AM, Chiusa L, Repici A, Mioli P, et al. Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis. World J Gastroenterol. 2006;12:6172–6177. - PMC - PubMed
    1. Pasricha PJ, Pehlivanov ND, Gomez G, Vittal H, Lurken MS, Farrugia G. Changes in the gastric enteric nervous system and muscle: a case report on two patients with diabetic gastroparesis. BMC Gastroenterol. 2008;8:21. - PMC - PubMed
    1. Iwasaki H, Kajimura M, Osawa S, Kanaoka S, Furuta T, Ikuma M, Hishida A. A deficiency of gastric interstitial cells of Cajal accompanied by decreased expression of neuronal nitric oxide synthase and substance P in patients with type 2 diabetes mellitus. J Gastroenterol. 2006;41:1076–1087. - PubMed

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