Document Detail


Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C(high) CCR2(+) inflammatory monocyte/macrophage-derived CCL11.
MedLine Citation:
PMID:  21498668     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent genome-wide association studies of pediatric inflammatory bowel disease have implicated the 17q12 loci, which contains the eosinophil-specific chemokine gene CCL11, with early-onset inflammatory bowel disease susceptibility. In the current study, we employed a murine model of experimental colitis to define the molecular pathways that regulate CCL11 expression in the chronic intestinal inflammation and pathophysiology of experimental colitis. Bone marrow chimera experiments showed that hematopoietic cell-derived CCL11 is sufficient for CCL11-mediated colonic eosinophilic inflammation. We show that dextran sodium sulfate (DSS) treatment promotes the recruitment of F4/80(+)CD11b(+)CCR2(+)Ly6C(high) inflammatory monocytes into the colon. F4/80(+)CD11b(+)CCR2(+)Ly6C(high) monocytes express CCL11, and their recruitment positively correlated with colonic eosinophilic inflammation. Phenotypic analysis of purified Ly6C(high) intestinal inflammatory macrophages revealed that these cells express both M1- and M2-associated genes, including Il6, Ccl4, Cxcl2, Arg1, Chi3l3, Ccl11, and Il10, respectively. Attenuation of DSS-induced F4/80(+)CD11b(+)CCR2(+)Ly6C(high) monocyte recruitment to the colon in CCR2(-/-) mice was associated with decreased colonic CCL11 expression, eosinophilic inflammation, and DSS-induced histopathology. These studies identify a mechanism for DSS-induced colonic eosinophilia mediated by Ly6C(high)CCR2(+) inflammatory monocyte/macrophage-derived CCL11.
Authors:
Amanda Waddell; Richard Ahrens; Kris Steinbrecher; Burke Donovan; Marc E Rothenberg; Ariel Munitz; Simon P Hogan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-15
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  186     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-04     Completed Date:  2011-07-05     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5993-6003     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD11b / immunology
Antigens, Differentiation / genetics
Antigens, Ly / analysis,  immunology
Bone Marrow Cells
Chemokine CCL11 / genetics,  immunology*,  metabolism
Colitis / chemically induced,  immunology*,  metabolism
Colon / immunology
Dextran Sulfate / pharmacology
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Eosinophilia / immunology*
Female
Gene Expression Regulation
Inflammatory Bowel Diseases / immunology*,  metabolism
Macrophages / cytology,  immunology
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Fluorescence
Monocytes / drug effects,  immunology
Polymerase Chain Reaction
Receptors, CCR2 / analysis,  immunology
Grant Support
ID/Acronym/Agency:
R01 AI045898/AI/NIAID NIH HHS; R01 AI045898-09/AI/NIAID NIH HHS; R01 AI073553/AI/NIAID NIH HHS; R01 AI073553/AI/NIAID NIH HHS; R01 AI073553-04/AI/NIAID NIH HHS; R01 AI45898/AI/NIAID NIH HHS; R01 DK090119/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD11b; 0/Antigens, Differentiation; 0/Antigens, Ly; 0/Ccl11 protein, mouse; 0/Ccr2 protein, mouse; 0/Chemokine CCL11; 0/Ly-6C antigen, mouse; 0/Receptors, CCR2; 0/monocyte-macrophage differentiation antigen; 9042-14-2/Dextran Sulfate
Comments/Corrections

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