Beyer Katharina, Poetschke Christian, Partecke Lars Ivo, von Bernstorff Wolfram, Maier Stefan, Broeker Barbara M, Heidecke Claus-Dieter
Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany.
Universitätsmedizin Greifswald, Klinik für Allgemein-, Viszeral-, Thorax- und Gefäβchirurgie, Greifswald, Germany; Universitätsmedizin Greifswald, Abteilung für Immunologie, Greifswald, Germany.
PLoS One. 2014 Jun 2;9(6):e97451. doi: 10.1371/journal.pone.0097451. eCollection 2014.
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.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）通过部分仍不明的机制影响多种炎症反应。TRAIL由免疫系统的多种细胞产生并表达。小鼠结肠升支支架性腹膜炎（CASP）是弥漫性腹膜炎的一种高炎症模型。正如我们之前所表明的，TRAIL能显著提高小鼠CASP模型的存活率。这伴随着相关淋巴组织中中性粒细胞浸润的显著减少。此外，已知TRAIL可诱导中性粒细胞凋亡，而中性粒细胞凋亡的加速可增强炎症反应的消退。在本研究中，我们调查了TRAIL在脓毒症中的保护作用与其对中性粒细胞的影响之间的相关性。我们发现浸润淋巴器官的中性粒细胞高密度表达TRAIL受体DR5。此外，我们证明TRAIL治疗可增强脾脏、肺和肝脏中中性粒细胞的凋亡，并减少脓毒症期间的器官损伤。为了进一步研究中性粒细胞在TRAIL介导的CASP保护作用中的作用，我们在CASP发生前24小时清除了中性粒细胞。在这些中性粒细胞减少的小鼠中，给予TRAIL无效。我们得出结论，TRAIL诱导组织浸润性中性粒细胞凋亡，从而保护器官免受脓毒症诱导的损伤。
