Frontline Science: Macrophage-derived exosomes promote neutrophil necroptosis following hemorrhagic shock

• DOI: 10.1189/jlb.3hi0517-173r
• Publication Date: 2017-08-12T00:25:27Z
• Authors: Yang Jiao; Zhigang Li; Patricia A Loughran; Erica K Fan; Melanie J Scott; Yuehua Li; Timothy R Billiar; Mark A Wilson; Xueyin Shi; Jie Fan
• Keywords: Inflammation; Male; 0301 basic medicine; Neutrophils; Primary Cell Culture; NADPH Oxidases; Shock, Hemorrhagic; Exosomes; Coculture Techniques; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Mice; Necrosis; 03 medical and health sciences; Macrophages, Alveolar; Animals; Humans; Reactive Oxygen Species

Abstract Hemorrhagic shock (HS) renders patients susceptible to development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction (MODS) through mechanisms that are, as yet, unclear. Cell necroptosis, a form regulated cell death, is one the controls release mediators from innate immune cells, such polymorphonuclear neutrophils (PMNs), critically regulates progress inflammation. In this study, we investigated alveolar macrophage (AMϕ) effects on PMN necroptosis following HS. With use in vivo ex HS models, reveal novel function shock-activated AMϕ promoting necroptosis. We demonstrate exosomes released HS-activated induce mainly NADPH oxidase-derived reactive oxygen species (ROS) production inside PMNs subsequent promotion These findings explore previously unidentified pathway AMϕ–PMN cross-talk, which causes enhanced exaggerated post-HS lung The targeting death may serve new therapeutic strategy for treatment SIRS.