Open AccessTRAIL Induces Neutrophil Apoptosis and Dampens Sepsis-Induced Organ Injury in Murine Colon Ascendens Stent Peritonitis
Author(s) -
Katharina Beyer,
Christian Poetschke,
Lars Ivo Partecke,
Wolfram von Bernstorff,
Stefan A. Maier,
B. M. Broeker,
Claus–Dieter Heidecke
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0097451
Subject(s) - apoptosis , sepsis , peritonitis , immune system , inflammation , tumor necrosis factor alpha , immunology , medicine , spleen , infiltration (hvac) , biology , biochemistry , physics , thermodynamics
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.