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Frontline Science: Macrophage‐derived exosomes promote neutrophil necroptosis following hemorrhagic shock
Author(s) -
Jiao Yang,
Li Zhigang,
Loughran Patricia A.,
Fan Erica K.,
Scott Melanie J.,
Li Yuehua,
Billiar Timothy R.,
Wilson Mark A.,
Shi Xueyin,
Fan Jie
Publication year - 2018
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.3hi0517-173r
Subject(s) - necroptosis , inflammation , biology , innate immune system , immunology , programmed cell death , microvesicles , macrophage , microbiology and biotechnology , immune system , nadph oxidase , apoptosis , reactive oxygen species , in vitro , microrna , biochemistry , gene
Hemorrhagic shock (HS) renders patients susceptible to development of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS) through mechanisms that are, as yet, unclear. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that controls cell release of inflammatory mediators from innate immune cells, such as polymorphonuclear neutrophils (PMNs), and critically regulates the progress of inflammation. In this study, we investigated the mechanisms of alveolar macrophage (AMϕ) effects on PMN necroptosis following HS. With the use of in vivo and ex vivo HS models, we reveal a novel function of shock‐activated AMϕ in promoting PMN necroptosis. We demonstrate that exosomes released from HS‐activated AMϕ induce mainly NADPH oxidase‐derived reactive oxygen species (ROS) production inside PMNs and subsequent promotion of necroptosis. These findings explore a previously unidentified pathway of AMϕ–PMN cross‐talk, which causes enhanced PMN necroptosis and subsequent exaggerated post‐HS lung inflammation. The targeting of this PMN death pathway may serve as a new therapeutic strategy for treatment of post‐HS SIRS.