Neutrophil extracellular traps induced by pro-inflammatory cytokines enhance procoagulant activity in NASH patients

Du, Jingwen; Zhang, Jinming; Chen, Xiaojing; Zhang, Shuoqi; Zhang, Cong; Liu, Huan; Li, Yueyue; Li, Mengdi; Wu, Xiaoming; Xiang, Mengqi; Wang, Chengyue; Liu, Langjiao; Wang, Chunli; Fang, Shaohong; Shi, Jialan

doi:10.1016/j.clinre.2021.101697

Cited by 24 publications

(20 citation statements)

References 33 publications

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“… 28 However, we could not assess and draw conclusions on the regulation of fibrinolysis, which in a recent study was found impaired in non-diabetic patients with NAFLD, 29 and on the role of neutrophil extracellular traps in triggering coagulation in participants with liver inflammation. 30 Notwithstanding, the present results seem to confirm that subclinical systemic inflammation (CRP levels) impact on the coagulation balance at different levels, 31 even in this cohort of apparently healthy and asymptomatic individuals, but most importantly showed that the association of early liver damage with procoagulant imbalance is independent of CRP. However, the association of low ferritin with reduced PC, going in the opposite direction of that of CRP and thereby likely reflecting a deficit in iron stores, seems novel and deserves further investigation.…”

Section: Discussionsupporting

confidence: 76%

Clinical and genetic determinants of the fatty liver–coagulation balance interplay in individuals with metabolic dysfunction

Valenti¹,

Tripodi²,

Mura³

et al. 2022

JHEP Reports

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Section: Discussionsupporting

confidence: 76%

Clinical and genetic determinants of the fatty liver–coagulation balance interplay in individuals with metabolic dysfunction

Valenti¹,

Tripodi²,

Mura³

et al. 2022

JHEP Reports

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Section: Neutrophils In Chronic Inflammationmentioning

confidence: 99%

“…MPO-DNA levels, which are a marker of NETs, are elevated in NASH patients and mouse models of NASH [ 101 , 102 ]. NETs derived from NASH patients increase thrombus formation and can induce a procoagulant phenotype in ECs [ 101 ]. In a mouse model of NASH, steatosis developed independently of NETs, which indicates that NET formation occurs as a consequence of fatty liver accumulation.…”

Section: Neutrophils In Chronic Inflammationmentioning

confidence: 99%

Neutrophils in chronic inflammatory diseases

2022

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Chronic inflammation is a component of many disease conditions that affect a large group of individuals worldwide. Chronic inflammation is characterized by persistent, low-grade inflammation and is increased in the aging population. Neutrophils are normally the first responders to acute inflammation and contribute to the resolution of inflammation. However, in chronic inflammation, the role of neutrophils is less well understood and has been described as either beneficial or detrimental, causing tissue damage and enhancing the immune response. Emerging evidence suggests that neutrophils are important players in several chronic diseases, such as atherosclerosis, diabetes mellitus, nonalcoholic fatty liver disease and autoimmune disorders. This review will highlight the interaction of neutrophils with other cells in the context of chronic inflammation, the contribution of neutrophils to selected chronic inflammatory diseases, and possible future therapeutic strategies.

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“…Kolaczkowska et al [ 16 ] found that intrahepatic neutrophil infiltration is critical for bacterial-induced liver injury, and liver injury decreased 80% when NET formation was inhibited in the liver. Similarly, NETs have been found to contribute to liver injury associated with sepsis that is induced by binge alcohol consumption [ 8 ], along with many other liver disorders not associated with alcohol, such as non-alcoholic steatohepatitis, ischemia reperfusion injury, and portal hypertension [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

et al. 2022

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Background/Aims: Binge drinking leads to many disorders, including alcoholic hepatosteatosis, which is characterized by intrahepatic neutrophil infiltration and increases the risk of hepatocellular carcinoma (HCC). Molecular mechanisms may involve the migration of bacterial metabolites from the gut to the liver and the activation of neutrophil extracellular traps (NETs).Methods: Serum samples from both binge drinking and alcohol-avoiding patients were analyzed. Mouse models of chronic plus binge alcohol-induced hepatosteatosis and HCC models were used.Results: A marker of NETs formation, lipopolysaccharide (LPS), was significantly higher in alcoholic hepatosteatosis and HCC patients and mice than in controls. Intrahepatic inflammation markers and HCC-related cytokines were decreased in mice with reduced NET formation due to neutrophil elastase (NE) deletion, and liver-related symptoms of alcohol were also alleviated in NE knockout mice. Removal of intestinal bacteria with antibiotics led to decreases in markers of NETs formation and inflammatory cytokines upon chronic alcohol consumption, and development of alcoholic hepatosteatosis and HCC was also attenuated. These functions were restored upon supplementation with the bacterial product LPS. When mice lacking toll-like receptor 4 (TLR4) received chronic alcohol feeding, intrahepatic markers of NETs formation decreased, and hepatosteatosis and HCC were alleviated.Conclusions: Formation of NETs following LPS stimulation of TLR4 upon chronic alcohol use leads to increased alcoholic steatosis and subsequent HCC.

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Neutrophil extracellular traps induced by pro-inflammatory cytokines enhance procoagulant activity in NASH patients

Cited by 24 publications

References 33 publications

Clinical and genetic determinants of the fatty liver–coagulation balance interplay in individuals with metabolic dysfunction

Clinical and genetic determinants of the fatty liver–coagulation balance interplay in individuals with metabolic dysfunction

Neutrophils in chronic inflammatory diseases

Gut-derived lipopolysaccharide promotes alcoholic hepatosteatosis and subsequent hepatocellular carcinoma by stimulating neutrophil extracellular traps through toll-like receptor 4

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