Document Detail

Inhibition of macrophage function prevents intestinal inflammation and postoperative ileus in rodents.
MedLine Citation:
PMID:  16809419     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Abdominal surgery results in a molecular and cellular inflammatory response in the intestine, leading to postoperative ileus. It was hypothesised that resident macrophages within the intestinal muscularis have an important role in this local inflammation. AIMS: To investigate whether chemical or genetic depletion of resident muscularis macrophages would lead to a reduction in the local inflammation and smooth-muscle dysfunction. METHODS: Two rodent models were used to deplete and inactivate macrophages: (1) a rat model in which resident macrophages were depleted by chlodronate liposomes; (2) a model of mice with osteopetrosis mice, completely lacking the resident muscularis macrophages, used as an additional genetic approach. Animals with normal or altered intestinal macrophages underwent surgical intestinal manipulation. The inflammatory response was investigated by quantitative reverse transcriptase-polymerase chain reaction for mRNA of MIP-1alpha, interleukin (IL)1beta, IL6, intracellular adhesion molecule 1 (ICAM-1) and monocyte chemotractant protein 1 (MCP)-1 in the isolated small bowel muscularis. In addition, muscularis whole mounts were used for histochemical and immunohistochemical analysis to quantify leucocyte infiltration and detect cytokine expression. Subsequently, in vitro muscle contractility and in vivo gastrointestinal transit were measured. RESULTS: Both models resulted in markedly decreased expression of MIP-1alpha, IL1beta, IL6, ICAM-1 and MCP-1 after manipulation compared with controls. In addition to this decrease in inflammatory mediators, recruitment of leucocytes into the muscularis was also diminished. Macrophage-altered animals had near normal in vitro jejunal circular muscle function and gastrointestinal transit despite surgical manipulation. CONCLUSIONS: Resident intestinal muscularis macrophages are initially involved in inflammatory responses resulting in postoperative ileus. Depletion and inactivation of the muscularis macrophage network prevents postoperative ileus.
Sven Wehner; Florian F Behrendt; Boris N Lyutenski; Mariola Lysson; Anthony J Bauer; Andreas Hirner; Jörg C Kalff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-06-29
Journal Detail:
Title:  Gut     Volume:  56     ISSN:  0017-5749     ISO Abbreviation:  Gut     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-16     Completed Date:  2007-10-23     Revised Date:  2010-09-15    
Medline Journal Info:
Nlm Unique ID:  2985108R     Medline TA:  Gut     Country:  England    
Other Details:
Languages:  eng     Pagination:  176-85     Citation Subset:  AIM; IM    
Department of Surgery, University of Bonn, Bonn 53105, Germany.
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MeSH Terms
Chemokine CCL2 / analysis
Gastrointestinal Motility / immunology
Ileus / immunology,  prevention & control*
Immunohistochemistry / methods
Intercellular Adhesion Molecule-1 / analysis
Interleukin-1beta / analysis
Interleukin-6 / analysis
Intestine, Small / immunology
Macrophage Activation / immunology
Macrophages / immunology*
Muscle Contraction / immunology
Muscle, Smooth / immunology
Muscular Diseases / immunology,  prevention & control*
Postoperative Complications / immunology,  prevention & control*
RNA, Messenger / analysis
Rats, Sprague-Dawley
Reg. No./Substance:
0/Chemokine CCL2; 0/Interleukin-1beta; 0/Interleukin-6; 0/RNA, Messenger; 126547-89-5/Intercellular Adhesion Molecule-1

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

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