Emerging mechanisms of immunocoagulation in sepsis and septic shock

Tang, Daolin; Wang, Haichao; Billiar, Timothy R.; Kroemer, Guido; Kang, Rui

doi:10.1016/j.it.2021.04.001

Cited by 74 publications

(54 citation statements)

References 135 publications

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“…Various studies demonstrated that the early cytokine storm in Gram-negative sepsis activates a systemic coagulation cascade, which leads to formation of microthrombi throughout host circulation, and progress to life-threatening disseminated intravascular coagulation (DIC) 2 , 3 . Given the essential role of the aberrant coagulopathy in promoting organ dysregulation, we next asked whether transferring LPS-primed neutrophils affected the DIC progression in septic mice.…”

Section: Resultsmentioning

confidence: 99%

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Neutrophils restrain sepsis associated coagulopathy via extracellular vesicles carrying superoxide dismutase 2 in a murine model of lipopolysaccharide induced sepsis

et al. 2022

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Disseminated intravascular coagulation (DIC) is a complication of sepsis currently lacking effective therapeutic options. Excessive inflammatory responses are emerging triggers of coagulopathy during sepsis, but the interplay between the immune system and coagulation are not fully understood. Here we utilize a murine model of intraperitoneal lipopolysaccharide stimulation and show neutrophils in the circulation mitigate the occurrence of DIC, preventing subsequent septic death. We show circulating neutrophils release extracellular vesicles containing mitochondria, which contain superoxide dismutase 2 upon exposure to lipopolysaccharide. Extracellular superoxide dismutase 2 is necessary to induce neutrophils’ antithrombotic function by preventing endothelial reactive oxygen species accumulation and alleviating endothelial dysfunction. Intervening endothelial reactive oxygen species accumulation by antioxidants significantly ameliorates disseminated intravascular coagulation improving survival in this murine model of lipopolysaccharide challenge. These findings reveal an interaction between neutrophils and vascular endothelium which critically regulate coagulation in a model of sepsis and may have potential implications for the management of disseminated intravascular coagulation.

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Section: Resultsmentioning

confidence: 99%

“…As a result, DIC is usually manifested as thrombosis and bleeding at the same time. The resultant microinfarction, tissue hypoxia and hemorrhagic diathesis in DIC together promote further inflammation, exacerbate organ dysfunction and drive the occurrence of multiorgan failure 3 .…”

Section: Introductionmentioning

confidence: 99%

Neutrophils restrain sepsis associated coagulopathy via extracellular vesicles carrying superoxide dismutase 2 in a murine model of lipopolysaccharide induced sepsis

et al. 2022

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“…The release and activation of F3 (the main initiator of coagulation) from myeloid or epithelial cells is facilitated by activating inflammasomes and consequent gasdermin D (GSDMD)-mediated pyroptosis, coupled to signal through HMGB1, stimulator of interferon response CGAMP interactor 1 (STING1), or sequestosome 1 (SQSTM1) ( 166 ). Extracellular HMGB1 markedly increases the procoagulant activity of tissue factor by promoting the externalization of phosphatidylserine to the outer cell surface.…”

Section: Hmgs In Sepsismentioning

confidence: 99%

High Mobility Group Proteins in Sepsis

Liang

2022

Front. Immunol.

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Sepsis, a systemic inflammatory response disease, is the most severe complication of infection and a deadly disease. High mobility group proteins (HMGs) are non-histone nuclear proteins binding nucleosomes and regulate chromosome architecture and gene transcription, which act as a potent pro-inflammatory cytokine involved in the delayed endotoxin lethality and systemic inflammatory response. HMGs increase in serum and tissues during infection, especially in sepsis. A growing number of studies have demonstrated HMGs are not only cytokines which can mediate inflammation, but also potential therapeutic targets in sepsis. To reduce sepsis-related mortality, a better understanding of HMGs is essential. In this review, we described the structure and function of HMGs, summarized the definition, epidemiology and pathophysiology of sepsis, and discussed the HMGs-related mechanisms in sepsis from the perspectives of non-coding RNAs (microRNA, long non-coding RNA, circular RNA), programmed cell death (apoptosis, necroptosis and pyroptosis), drugs and other pathophysiological aspects to provide new targets and ideas for the diagnosis and treatment of sepsis.

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“…65 Bacterial infection such as S. aureus and Streptococcus pneumoniae, as well as E. coli can lead to sepsis. 66,67 In addition, the activation of the MAPK and NF-κB signaling pathways and the secretion of TNF-α and IL-6 in macrophages engage in lung injury induced by bacterial infection or sepsis. 68,69 Previous studies and the present study indicate that the MAPK signaling pathway, the NF-κB signaling pathway, IL-6 and TNF-α engage in ALI, and that CPPS is able to regulate MAPK signaling pathway and NF-κB signaling pathway activation and cytokine secretion, which might explain the mechanism of CPPS attenuating E. coli-induced ALI.…”

Section: Papermentioning

confidence: 99%