Sera from Septic Patients Contain the Inhibiting Activity of the Extracellular ATP-Dependent Inflammasome Pathway
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- Ho Van Minh
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Hirohashi Nobuyuki
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Kong Weng-Sheng
- Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Yun Guo
- Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Ota Kohei
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Itai Junji
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Yamaga Satoshi
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Suzuki Kei
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
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- Tanigawa Koichi
- Fukushima Global Medical Science Center, Fukushima Medical University
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- Kanno Masamoto
- Department of Immunology, Graduate School of Biomedical and Health Sciences, Hiroshima University Core Research for Evolutionary Science and Technology, Japan Agency for Medical Research and Development Core Development of Advanced Measurement and Analysis Systems, Japan Agency for Medical Research and Development
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- Shime Nobuaki
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University
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Abstract
<p>Immunoparalysis is a common cause of death for critical care patients with sepsis, during which comprehensive suppression of innate and adaptive immunity plays a significant pathophysiological role. Although the underlying mechanisms are unknown, damage-associated molecular patterns (DAMPs) from septic tissues might be involved. Therefore, we surveyed sera from septic patients for factors that suppress the innate immune response to DAMPs, including adenosine triphosphate (ATP), monosodium urate, and high mobility group box-1. Macrophages, derived from THP-1 human acute monocytic leukemia cells, were incubated with each DAMP, in the presence or absence of sera that were collected from critically ill patients. Secreted cytokines were then quantified, and cell lysates were assayed for relevant intracellular signaling mediators. Sera from septic patients who ultimately did not survive significantly suppressed IL-1β production only in response to extracellular ATP. This effect was most pronounced with sera collected on day 3, and persisted with sera collected on day 7. However, this effect was not observed when THP-1 cells were treated with sera from survivors of sepsis. Septic sera collected at the time of admission (day 1) also diminished intracellular levels of inositol 1,4,5-triphosphate and cytosolic calcium (P < 0.01), both of which are essential for ATP signaling. Finally, activated caspase-1 was significantly diminished in cells exposed to sera collected on day 7 (P < 0.05). In conclusion, the sera of septic patients contain certain factors that persistently suppress the immune response to extracellular ATP, thereby leading to adverse clinical outcomes.</p>
Journal
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 245 (3), 193-204, 2018
Tohoku University Medical Press