title: Neutrophil extracellular traps contribute to the intestine damage in endotoxemic rats.
abstract: BACKGROUND
  Sepsis is one of the most troublesome problems in critically ill patients and often accompanied with multiple organ dysfunction and high mortality. Gut injury or dysfunction may contribute to the pathogenesis of sepsis. Neutrophil extracellular traps (NETs) do not only kill microorganisms but also damage host cells during inflammatory response to infection. The aim of this study was to investigate whether NETs are capable of promoting the impairment of the gut in a rat model of lipopolysaccharide (LPS)-induced sepsis.
  
  
  METHODS
  The sepsis model was induced in rats by intraperitoneal injection of LPS (10 mg/kg). All rats were divided into three groups as follows: 1) control group; 2) LPS group; and 3) LPS + DNase I group. The DNase I solution (10 mg/kg) was injected intravenously to disrupt NETs 30 min after the LPS treatment. The animals were sacrificed at 3 h and 24 h after LPS or saline challenge. The intestinal cell apoptosis was examined by detecting the level of cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. The length and morphology of Villi were assessed histologically through hematoxylin and eosin stain. The levels of tumor necrosis factor-alpha and interleukin-10 in serum and intestine were detected by enzyme-linked immunosorbent assay. Intestinal injury was evaluated with Chiu scoring system.
  
  
  RESULTS
  A large number of neutrophils infiltrated were activated to release NETs in the intestine of LPS-induced septic rats. The disruption of NETs reduced the acute systemic inflammatory response and apoptosis of intestinal epithelial cells and alleviated histologic pathogenesis. Removal of NETs provided a beneficial effect on intestinal injury.
  
  
  CONCLUSIONS
  This study demonstrates that the release of NETs may contribute to the intestinal damage during sepsis.
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Shuangying
authors.initials: S
authors.lastname: Hao
authors.affiliation: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Yan
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: dingwei_nju@hotmail.com.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Ding
authors.affiliation: Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu Province, China. Electronic address: likuanyu@nju.edu.cn.
authors.forename: Kuanyu
authors.initials: K
authors.lastname: Li
authors.affiliation: Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Jieshou
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D065206:Extracellular Traps / Q000502:physiology*; D007410:Intestinal Diseases / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007422:Intestines / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides; D008297:Male; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D008070:Lipopolysaccharides
keywords: Apoptosis; Endotoxemia; Intestinal injury; Neutrophil extracellular traps (NETs); Sepsis