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

M. Grover, C. E. Bernard, Pankaj Jay Pasricha, H. P. Parkman, S. J. Gibbons, James A 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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalNeurogastroenterology and Motility
DOIs
StateAccepted/In press - 2016

Fingerprint

Gastroparesis
Pyloric Antrum
Interstitial Cells of Cajal
Macrophages
Anti-Inflammatory Agents
Gastric Emptying
Myenteric Plexus
Nitric Oxide Synthase Type I
Vasoactive Intestinal Peptide
Nuclear Medicine
Tyrosine 3-Monooxygenase
Substance P
Radionuclide Imaging
Biopsy
Muscles
Research
Population

Keywords

  • Enteric nervous system
  • Gastrointestinal motility
  • Immune cells
  • Interstitial cells of Cajal
  • Macrophages

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

Cite this

Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum. / Grover, M.; Bernard, C. E.; Pasricha, Pankaj Jay; Parkman, H. P.; Gibbons, S. J.; Tonascia, James A; 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.

In: Neurogastroenterology and Motility, 2016.

Research output: Contribution to journalArticle

Grover, M, Bernard, CE, Pasricha, PJ, Parkman, HP, Gibbons, SJ, Tonascia, JA, Koch, KL, Mccallum, RW, Sarosiek, I, Hasler, WL, Nguyen, LAB, Abell, TL, Snape, WJ, Kendrick, ML, Kellogg, TA, Mckenzie, TJ, Hamilton, FA & Farrugia, G 2016, 'Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum', Neurogastroenterology and Motility. https://doi.org/10.1111/nmo.13018
Grover, M. ; Bernard, C. E. ; Pasricha, Pankaj Jay ; Parkman, H. P. ; Gibbons, S. J. ; Tonascia, James A ; 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. / Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum. In: Neurogastroenterology and Motility. 2016.
@article{24c5fd7954c0437b9b57eee8b76c4451,
title = "Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum",
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",
author = "M. Grover and Bernard, {C. E.} and Pasricha, {Pankaj Jay} and Parkman, {H. P.} and Gibbons, {S. J.} and Tonascia, {James A} and Koch, {K. L.} and Mccallum, {R. W.} and I. Sarosiek and Hasler, {W. L.} and Nguyen, {L. A B} and Abell, {T. L.} and Snape, {W. J.} and Kendrick, {M. L.} and Kellogg, {T. A.} and Mckenzie, {T. J.} and Hamilton, {F. A.} and G. Farrugia",
year = "2016",
doi = "10.1111/nmo.13018",
language = "English (US)",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Diabetic and idiopathic gastroparesis is associated with loss of CD206-positive macrophages in the gastric antrum

AU - Grover, M.

AU - Bernard, C. E.

AU - Pasricha, Pankaj Jay

AU - Parkman, H. P.

AU - Gibbons, S. J.

AU - Tonascia, James A

AU - Koch, K. L.

AU - Mccallum, R. W.

AU - Sarosiek, I.

AU - Hasler, W. L.

AU - Nguyen, L. A B

AU - Abell, T. L.

AU - Snape, W. J.

AU - Kendrick, M. L.

AU - Kellogg, T. A.

AU - Mckenzie, T. J.

AU - Hamilton, F. A.

AU - Farrugia, G.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Enteric nervous system

KW - Gastrointestinal motility

KW - Immune cells

KW - Interstitial cells of Cajal

KW - Macrophages

UR - http://www.scopus.com/inward/record.url?scp=85009210660&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009210660&partnerID=8YFLogxK

U2 - 10.1111/nmo.13018

DO - 10.1111/nmo.13018

M3 - Article

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1350-1925

ER -