Premium
Human intestinal ischemia/reperfusion‐induced inflammation characterized: experiences from a new translational model
Author(s) -
Lenaerts Kaatje,
Grootjans Joep,
Derikx Joep PM,
Matthijsen Robert A,
Bruïne Adriaan P,
Bijnen Annemarie A,
Dam Ronald M,
Dejong Cornelis HC,
Buurman Wim A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.565.15
Subject(s) - ischemia , inflammation , western blot , reperfusion injury , complement system , chemistry , in vivo , jejunum , immunohistochemistry , medicine , immunology , andrology , pathology , endocrinology , biology , biochemistry , immune system , microbiology and biotechnology , gene
A new unique in vivo human model was used to investigate the inflammatory response following intestinal ischemia/reperfusion (I‐IR). In this model, an isolated part of jejunum, to be removed during a standard surgical procedure, was exposed to 45 minutes of ischemia, followed by 30 and 120 minutes of reperfusion. At all time points tissue and blood was collected. Histology revealed intestinal barrier integrity loss after ischemia, which further aggravated during reperfusion. This was reflected by massive leakage of intestinal fatty acid binding protein and soluble cytokeratin 18 (p<0.01) from damaged enterocytes, accompanied by increased arteriovenous concentration differences of endotoxin (p<0.05). Western blot for C3c and immunohistochemistry for activated C3 revealed complement activation after IR. During reperfusion, enhanced tissue mRNA expression of interleukin (IL)‐6 and IL‐8 (p<0.05) was accompanied by increased IL‐6 and IL‐8 release into the circulation (p<0.01). Furthermore, expression of intercellular adhesion molecule‐1 was markedly increased, facilitating the observed influx of neutrophils into damaged villus tips. This study shows for the first time the sequelae of human I‐IR‐induced inflammation, which is characterized by complement activation, production and release of cytokines into the circulation, endothelial activation, and neutrophil influx into IR‐damaged tissue.