Emerging mechanisms of immunocoagulation in sepsis and septic shock.

Emerging mechanisms of immunocoagulation in sepsis and septic shock.
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败血症和败血性休克中免疫凝的新兴机制。

DOI:
10.1016/j.it.2021.04.001
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发表时间:
2021-06
影响因子:
16.8
通讯作者:
Kang R
Kang R
中科院分区:
医学1区
文献类型:
--
作者:
Tang D;Wang H;Billiar TR;Kroemer G;Kang R

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由微生物感染引起的脓毒症和脓毒性休克仍然是最具挑战性的健康问题之一,每年在全球造成1100万人死亡。宿主对病原体感染的反应如何有效地恢复体内平衡,而不是诱发致病性和潜在致命的前馈反应?最近,我们对哺乳动物免疫和凝血(“免疫凝血”)之间的界面及其对脓毒症的影响的理解有了重大的新进展。特别地,F3(凝血的主要引发剂)从骨髓或上皮细胞释放和活化通过活化炎性小体和随后的GSDMD介导的焦亡来促进,其与经由HMGB1、STING1或SQSTM 1的信号传导偶联。免疫凝血途径的药理学调节成为脓毒症的新的和潜在的治疗策略。
Sepsis and septic shock driven by microbial infections are still among the most challenging health problems, causing 11 million deaths worldwide every year. How does the host’s response to pathogen infections effectively restore homeostasis instead of precipitating pathogenic and potentially fatal feedforward reactions? Recently there have been significant new advances in our understanding of the interface between mammalian immunity and coagulation (“immunocoagulation”) and its impact on sepsis. In particular, the release and activation of F3 (the main initiator of coagulation) from and on myeloid or epithelial cells is facilitated by activating inflammasomes and consequent GSDMD-mediated pyroptosis, coupled to signaling via HMGB1, STING1 or SQSTM1. Pharmacological modulation of the immunocoagulation pathways emerges as novel and potential therapeutic strategies for sepsis.
昼夜节律时钟控制脓毒症中的免疫检查点通路
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