Document Detail

Th2 cytokine-induced alterations in intestinal smooth muscle function depend on alternatively activated macrophages.
MedLine Citation:
PMID:  18471439     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: Enteric nematode infection induces a strong type 2 T helper cell (Th2) cytokine response characterized by increased infiltration of various immune cells, including macrophages. The role of these immune cells in host defense against nematode infection remains poorly defined. The present study investigated the role of macrophages and the arginase pathway in nematode-induced changes in intestinal smooth muscle function and worm expulsion.
METHODS: Mice were infected with Nippostrongylus brasiliensis and treated with clodronate-containing liposome to deplete macrophages or given S-(2-boronoethyl)-I-cysteine in drinking water to inhibit arginase activity. Segments of intestinal smooth muscle were suspended in organ baths to determine responses to acetylcholine, 5-hydroxytryptamine, or nerve stimulation. The phenotype of macrophages was monitored by measuring mRNA expression of the specific molecular markers by real-time polymerase chain reaction or viewed by immunofluorescence staining.
RESULTS: Infection increased the infiltration of macrophages and up-regulation alternatively activated macrophage markers by a mechanism dependent on interleukin-4 (IL-4) or interleukin-13 (IL-13) activation of signal transducer and activator of transcription 6. Elimination of alternatively activated macrophages blocked smooth muscle hypercontractility and the increased smooth muscle thickness, and impaired worm expulsion. In addition, specific inhibition of arginase activity interfered with smooth muscle contractility, but only partially affected the protective immunity of the host.
CONCLUSIONS: These data show that the phenotype of macrophages is determined by the local immune environment and that alternatively activated macrophages play a major role in the effects of Th2 cytokines, IL-4 and IL-13, on intestinal smooth muscle function.
Aiping Zhao; Joseph F Urban; Robert M Anthony; Rex Sun; Jennifer Stiltz; Nico van Rooijen; Thomas A Wynn; William C Gause; Terez Shea-Donohue
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-04-04
Journal Detail:
Title:  Gastroenterology     Volume:  135     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-07-08     Completed Date:  2008-08-08     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  217-225.e1     Citation Subset:  AIM; IM    
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MeSH Terms
Arginase / metabolism
Interleukin-13 / metabolism
Interleukin-4 / metabolism
Intestines / immunology*,  parasitology
Macrophages / immunology*,  parasitology
Mice, Inbred BALB C
Mice, Mutant Strains
Mice, SCID
Muscle, Smooth / immunology*,  parasitology
Strongylida Infections / immunology*
Th2 Cells / immunology*,  metabolism,  parasitology
Up-Regulation / immunology
Grant Support
R01 AI031678/AI/NIAID NIH HHS; R01 AI031678-12/AI/NIAID NIH HHS; R01 AI031678-13/AI/NIAID NIH HHS; R01 AI031678-14/AI/NIAID NIH HHS; R01 AI049316/AI/NIAID NIH HHS; R01 AI049316-07/AI/NIAID NIH HHS; R01 AI049316-08/AI/NIAID NIH HHS; R01 DK083418/DK/NIDDK NIH HHS; R01-AI/DK49316/AI/NIAID NIH HHS; R01-AI031678/AI/NIAID NIH HHS; T32 DK067872/DK/NIDDK NIH HHS
Reg. No./Substance:
0/Interleukin-13; 207137-56-2/Interleukin-4; EC

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