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The Kupffer Cell Inhibition Exacerbates but Splenectomy Prevents Mortality in a Rat Septic Peritonitis Model
- Source :
- Journal of Surgical Research. 175:101-112
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Objective The purpose of this study was to investigate whether inhibition of Kupffer cells (KCs) affects the expression of high mobility group box 1 (HMGB1) and mortality in septic peritonitis. The role of the spleen in septic peritonitis was also investigated. Methods Rats were given liposome-entrapped dichloromethylene diphosphonate (lipo-MDP) to eliminate KCs or non-entrapped liposome (lipo) before cecal ligation and puncture (CLP), and serum HMGB1 levels and mortality were assessed after CLP. Furthermore, KCs and tissue macrophages were isolated, and production of HMGB1 was investigated. Effects of splenectomy on serum HMGB1 levels and mortality were also investigated after CLP. Results Elimination of the Kupffer cells by lipo-MDP increased serum HMGB1 concentrations and mortality significantly. Furthermore, HMGB1 expression in both the periportal area of the liver and the spleen was greater in the lipo-MDP group than the lipo group. On the other hand, splenectomy blunted serum HMGB1 levels and improved mortality after CLP. The HMGB1 expression was greater in the spleen compared with the liver after CLP. Furthermore, production of HMGB1 was greatest in splenic macrophages in vitro . The number of ED3-positive cells increased significantly in non-splenectomized animals but not in splenectomized animals after CLP. In the lipo-MDP treated groups, the number of ED3-positive macrophages also increased in the liver from non-splenectomized animals but not in the splenectomized animals after CLP. Conclusions The liver and the spleen play key roles in host defense during septic peritonitis. Migrating macrophages into the liver are, in part, derived from the spleen after CLP.
- Subjects :
- Male
Kupffer Cells
medicine.medical_treatment
Splenectomy
Peritonitis
chemical and pharmacologic phenomena
Spleen
Lung injury
HMGB1
digestive system
Rats, Sprague-Dawley
Sepsis
Andrology
medicine
Animals
HMGB1 Protein
biology
business.industry
Kupffer cell
bacterial infections and mycoses
medicine.disease
Rats
Disease Models, Animal
stomatognathic diseases
medicine.anatomical_structure
Cytokine
Immunology
biology.protein
Surgery
business
Subjects
Details
- ISSN :
- 00224804
- Volume :
- 175
- Database :
- OpenAIRE
- Journal :
- Journal of Surgical Research
- Accession number :
- edsair.doi.dedup.....3376df92d679834948bd8a022837b0ea