Document Detail


CD206-positive M2 macrophages that express heme oxygenase-1 protect against diabetic gastroparesis in mice.
MedLine Citation:
PMID:  20178793     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Gastroparesis is a well-recognized complication of diabetes. In diabetics, up-regulation of heme oxygenase-1 (HO1) in gastric macrophages protects against oxidative stress-induced damage. Loss of up-regulation of HO1, the subsequent increase in oxidative stress, and loss of Kit delays gastric emptying; this effect is reversed by induction of HO1. Macrophages have pro- and anti-inflammatory activities, depending on their phenotype. We investigated the number and phenotype of gastric macrophages in NOD/ShiLtJ (nonobese diabetic [NOD]) mice after onset of diabetes, when delayed gastric emptying develops, and after induction of HO1 to reverse delay.
METHODS: Four groups of NOD and db/db mice were studied: nondiabetic, diabetic with normal emptying, diabetic with delayed gastric emptying, and diabetic with delayed gastric emptying reversed by the HO1 inducer hemin. Whole mount samples from stomach were labeled in triplicate with antisera against F4/80, HO1, and CD206, and macrophages were quantified in stacked confocal images. Markers for macrophage subtypes were measured by quantitative polymerase chain reaction.
RESULTS: Development of diabetes was associated with an increased number of macrophages and up-regulation of HO1 in CD206(+) M2 macrophages. Onset of delayed gastric emptying did not alter the total number of macrophages, but there was a selective loss of CD206(+)/HO1(+) M2 macrophages. Normalization of gastric emptying was associated with repopulation of CD206(+)/HO1(+) M2 macrophages.
CONCLUSIONS: CD206(+) M2 macrophages that express HO1 appear to be required for prevention of diabetes-induced delayed gastric emptying. Induction of HO1 in macrophages might be a therapeutic option for patients with diabetic gastroparesis.
Authors:
Kyoung Moo Choi; Purna C Kashyap; Nirjhar Dutta; Gary J Stoltz; Tamas Ordog; Terez Shea Donohue; Anthony J Bauer; David R Linden; Joseph H Szurszewski; Simon J Gibbons; Gianrico Farrugia
Related Documents :
11007633 - Influence of metabolic state and diabetes on the outcome at the end of first year after...
8455073 - Characterization of gastric antral motility disturbances in diabetes using a scintigrap...
11007633 - Influence of metabolic state and diabetes on the outcome at the end of first year after...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-02-20
Journal Detail:
Title:  Gastroenterology     Volume:  138     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-10     Completed Date:  2010-07-01     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2399-409, 2409.e1     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Affiliation:
Enteric Neuroscience Program and Department of Physiology, Mayo Clinic, Rochester, Minnesota, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Arginase / genetics
Blood Glucose / analysis
Diabetes Complications / prevention & control*
Female
Gastric Emptying
Gastroparesis / prevention & control*
Heme Oxygenase-1 / analysis,  physiology*
Interleukin-10 / genetics
Lectins, C-Type / analysis*
Macrophages / enzymology,  physiology*
Mannose-Binding Lectins / analysis*
Membrane Proteins / analysis,  physiology*
Mice
Mice, Inbred NOD
Receptors, Cell Surface / analysis*
Grant Support
ID/Acronym/Agency:
DK57061/DK/NIDDK NIH HHS; DK68055/DK/NIDDK NIH HHS; P01 DK068055-050001/DK/NIDDK NIH HHS; R01 DK057061-09/DK/NIDDK NIH HHS; R01 DK057061-12/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Lectins, C-Type; 0/Mannose-Binding Lectins; 0/Membrane Proteins; 0/Receptors, Cell Surface; 0/mannose receptor; 130068-27-8/Interleukin-10; EC 1.14.99.3/Heme Oxygenase-1; EC 1.14.99.3/Hmox1 protein, mouse; EC 3.5.3.1/Arg1 protein, mouse; EC 3.5.3.1/Arginase
Comments/Corrections
Comment In:
Gastroenterology. 2010 Jun;138(7):2219-23   [PMID:  20434508 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Fibrin Glue is Effective Healing Perianal Fistulas in Patients with Crohn's Disease.
Next Document:  Low bone mass and severity of cholestasis affect fracture risk in patients with primary biliary cirr...