title: TRAIL induces neutrophil apoptosis and dampens sepsis-induced organ injury in murine colon ascendens stent peritonitis.
abstract: TNF-related apoptosis inducing ligand (TRAIL) influences several inflammatory reactions by partially still unknown mechanisms. TRAIL is produced and expressed by several cells of the immune system. Murine Colon Ascendens Stent Peritonitis (CASP) represents a hyperinflammatory model of diffuse peritonitis. As we have shown previously, TRAIL strongly improves survival in murine CASP. This is accompanied by a significantly reduced infiltration of neutrophils in the associated lymphoid tissue. Additionally, it is known that TRAIL induces apoptosis in neutrophils and acceleration of neutrophil apoptosis enhances resolution of inflammatory reactions. In this study, we investigated the correlation of the protective effect of TRAIL in sepsis and its influence on neutrophils. We found that neutrophils infiltrating the lymphoid organs express the TRAIL-receptor DR5 at high density. Furthermore, we demonstrated that TRAIL-treatment enhances apoptosis of neutrophils in the spleen, lung and liver and decreases organ injury during sepsis. To further examine a role for neutrophils in TRAIL-mediated protection in CASP, we have depleted neutrophils 24 hours prior to CASP. In these depleted mice, administration of TRAIL was ineffective. We conclude that TRAIL induces apoptosis in tissue-infiltrating neutrophils thereby protecting organs from sepsis-induced injury.
authors.affiliation: Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Beyer
authors.affiliation: Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany; Universitätsmedizin Greifswald, Abteilung für Immunologie, Greifswald, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Poetschke
authors.affiliation: Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany.
authors.forename: Lars Ivo
authors.initials: LI
authors.lastname: Partecke
authors.affiliation: Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: von Bernstorff
authors.affiliation: Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Maier
authors.affiliation: Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany; Universitätsmedizin Greifswald, Abteilung für Immunologie, Greifswald, Germany.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Broeker
authors.affiliation: Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany.
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Heidecke
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D008070:Lipopolysaccharides; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009928:Organ Specificity / Q000187:drug effects*; D010538:Peritonitis / Q000150:complications / Q000473:pathology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D018805:Sepsis / Q000150:complications / Q000473:pathology*; D013154:Spleen / Q000473:pathology; D015607:Stents / Q000009:adverse effects; D016019:Survival Analysis; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D008070:Lipopolysaccharides; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase