Neutrophil Infiltration as an Important Factor in Liver Ischemia and Reperfusion Injury

Suzuki, Shohachi; Toledo-Pereyra, L. H.; Rodriguez, F. J.; Cejalvo‐Lapeña, Dolores

doi:10.1097/00007890-199306000-00011

Cited by 738 publications

(61 citation statements)

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“…OLT histology and IRI grading. Formalin-fixed, paraffin-embedded liver sections (5-μm-thick) were stained with H&E. The severity of IRI was graded using Suzuki's criteria (69).…”

Section: Discussionmentioning

confidence: 99%

Antibiotic pretreatment alleviates liver transplant damage in mice and humans

Nakamura¹,

Kageyama²,

Itô³

et al. 2019

Journal of Clinical Investigation

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ResultsRecipient Abx pretreatment attenuates, but adjunctive fecal microbiota transfer recreates, hepatic IRI in mouse allogeneic OLT. We first aimed to determine the influence of Abx treatment on IRI severity in a clinically relevant allogeneic mouse OLT model (BALB/c> C57BL/6) with ex vivo cold storage (4°C for 18 hours), which mimics marginal human liver grafts. Mouse OLT recipients pretreated for 10 days (14, 15) with oral Abx (amoxicillin, 50 mg/mL) showed decreased serum aspartate aminotransferase (sAST) levels (OLT = 7047 ± 1332 vs. OLT + Abx = 3609 ± 447 IU/L, P = 0.0317; Figure 1A); attenuated sinusoidal congestion, edema/vacuolization and hepatocellular necrosis ( Figure 1B); decreased Suzuki's histological grading of IRI (OLT = 6.8 ± 0.6 vs. OLT + Abx = 3.6 ± 0.5, P

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“…OLT histology and IRI grading. Formalin-fixed, paraffin-embedded liver sections (5-μm-thick) were stained with H&E. The severity of IRI was graded using Suzuki's criteria (69).…”

Section: Discussionmentioning

confidence: 99%

Antibiotic pretreatment alleviates liver transplant damage in mice and humans

Nakamura¹,

Kageyama²,

Itô³

et al. 2019

Journal of Clinical Investigation

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“…The severity of liver IRI was assessed blindly and graded according to Suzuki's criteria on a scale from 0 to 4. No necrosis, congestion, or centrolobular ballooning is given a score of 0, while severe congestion and greater than 60% lobular necrosis is given a value of 4 (17).…”

Section: Methodsmentioning

confidence: 99%

“…It involves a local innate immune sterile inflammation-dominated response, driven by a cascade of free radicals, specifically reactive oxygen species (ROS) that ensue upon reintroduction of oxygen into the ischemic tissues. The degree of tissue damage depends on the extent and duration of the ischemia, the magnitude of the inflammatory response, mostly comprised of infiltrating macrophages and neutrophils, and the upregulation of cytoprotective mechanisms (17,18). We have previously reported that HO-1 is highly induced after liver IRI and that global HO-1 deficiency, as in systemic HO-1 heterozygous knockout mice, results in marked enhancement of hepatic IRI (19).…”

Section: Introductionmentioning

confidence: 99%

Myeloid HO-1 modulates macrophage polarization and protects against ischemia-reperfusion injury

Zhang¹,

Nakamura

Kageyama

et al. 2018

JCI Insight

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“…The severity of IRI was graded using Suzuki’s criteria on a scale from 0 to 4 52 . In this classification, no necrosis, congestion, or centrilobular ballooning is given a score of 0, while severe congestion and ballooning degeneration and >60% lobular necrosis is given a value of 4.…”

Section: Methodsmentioning

confidence: 99%

Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF-1α signaling pathway in liver inflammatory injury

et al. 2018

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Activating transcription factor 3 (ATF3) is a stress-induced transcription factor that plays important roles in regulating immune and metabolic homeostasis. Activation of the mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor (HIF) transcription factors are crucial for the regulation of immune cell function. Here, we investigated the mechanism by which the ATF3/mTOR/HIF-1 axis regulates immune responses in a liver ischemia/reperfusion injury (IRI) model. Deletion of ATF3 exacerbated liver damage, as evidenced by increased levels of serum ALT, intrahepatic macrophage/neutrophil trafficking, hepatocellular apoptosis, and the upregulation of pro-inflammatory mediators. ATF3 deficiency promoted mTOR and p70S6K phosphorylation, activated high mobility group box 1 (HMGB1) and TLR4, inhibited prolyl-hydroxylase 1 (PHD1), and increased HIF-1α activity, leading to Foxp3 downregulation and RORγt and IL-17A upregulation in IRI livers. Blocking mTOR or p70S6K in ATF3 knockout (KO) mice or bone marrow-derived macrophages (BMMs) downregulated HMGB1, TLR4, and HIF-1α and upregulated PHD1, increasing Foxp3 and decreasing IL-17A levels in vitro. Silencing of HIF-1α in ATF3 KO mice ameliorated IRI-induced liver damage in parallel with the downregulation of IL-17A in ATF3-deficient mice. These findings demonstrated that ATF3 deficiency activated mTOR/p70S6K/HIF-1α signaling, which was crucial for the modulation of TLR4-driven inflammatory responses and T cell development. The present study provides potential therapeutic targets for the treatment of liver IRI followed by liver transplantation.

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Neutrophil Infiltration as an Important Factor in Liver Ischemia and Reperfusion Injury

Cited by 738 publications

References 0 publications

Antibiotic pretreatment alleviates liver transplant damage in mice and humans

Antibiotic pretreatment alleviates liver transplant damage in mice and humans

Myeloid HO-1 modulates macrophage polarization and protects against ischemia-reperfusion injury

Loss of ATF3 exacerbates liver damage through the activation of mTOR/p70S6K/ HIF-1α signaling pathway in liver inflammatory injury

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