Signaling Pathways in Liver Diseases Kupffer Cells

Steib, Christian; Gerbes, Alexander L.

doi:10.1007/978-3-642-00150-5_4

Cited by 6 publications

(5 citation statements)

References 87 publications

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“…The phagocytosis of bacterial products in the liver is predominantly dependent on the activity of Kupffer cells (KCs), which are hepatic macrophages. 14,15 Therefore, KCs could have a leading role in the regulation of infection-related variceal bleeding, as proposed previously. 16 The activation of KCs is dependent on surface receptors such as Toll-like receptors (TLRs) and intracellular effectors such as MyD88.…”

mentioning

confidence: 70%

Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis

Steib¹,

Hartmann²,

Hesler³

et al. 2010

Laboratory Investigation

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Recent studies have shown that the risk of variceal bleeding in patients with liver cirrhosis increases with infections such as spontaneous bacterial peritonitis (SBP). In this study, we hypothesized that pretreatment with intraperitoneal LPS may escalate portal hypertension. In fibrotic livers (4 weeks after bile duct ligation, BDL), the activation of Kupffer cells (KCs) by zymosan (150 mg/ml) in the isolated non-recirculating liver perfusion system resulted in a transient increase in portal perfusion pressure. Pretreatment with intraperitoneal LPS (1 mg/kg body weight (b.w.) for 3 h) increased basal portal perfusion pressure, and prolonged the zymosan-induced increase from transient to a long-lasting increase that was sustained until the end of the experiments in BDL but not in sham-operated animals. Pretreatment with gadolinium chloride (10 mg/kg b.w.), MK-886 (0.6 mg/kg b.w.), Ly171883 (20 mM) or BM 13.177 (20 mM) reduced the maximal and long-lasting pressure increase in BDL animals by approximately 50-60%. The change in portal perfusion pressure was paralleled by a long-lasting production of cysteinyl leukotriene (Cys-LT) and thromboxane (TX) after LPS pretreatment. However, the response to vasoconstrictors was not altered by intraperitoneal LPS. Western blot analyses showed an increased Toll-like receptor (TLR)4 and MyD88 expression after LPS pretreatment. In vivo experiments confirmed that intraperitoneal LPS increased basal portal pressure, and extended the portal pressure increase produced by intraportal zymosan or by LPS infusion. In conclusion, upregulation of TLR4 and MyD88 expression in fibrotic livers confers hypersensitivity to LPS. This may lead to escalation of portal hypertension by production of TX and Cys-LT after endotoxin-induced KC activation. Therefore, LT inhibitors may represent a promising treatment option in addition to early administration of antibiotics in SBP.

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confidence: 70%

Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis

Steib¹,

Hartmann²,

Hesler³

et al. 2010

Laboratory Investigation

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“…It was concluded that Kupffer cell metabolites released in response to silica were toxic to hepatocytes. The involvement of Kupffer cells in the pathogenesis of liver injury mediated by chemicals is well documented, [58][59][60] and might be important in ENP-mediated liver damage as well.…”

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confidence: 99%

Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

Watson¹,

Molina²,

Louzada³

et al. 2015

IJN

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Background Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration. Materials and methods First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65 ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa . Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively. Results We found that the liver was the major site of initial uptake of 65 ZnO ENPs. There was a time-dependent decrease in tissue levels of 65 Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P . aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver. Conclusion Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that diminished Kupffer cell organelle motion correlated with ZnO ENP-induced liver injury.

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“…KC account for approximately 10–15% of the total liver cell population and represent 80–90% of tissue macrophages in the reticuloendothelial system. KC represent an important component of innate immunity 1 2. One characteristic of innate immunity is the rapid response to potentially dangerous stimuli.…”

mentioning

confidence: 99%

Kupffer cell activation and portal hypertension

Steib

2011

Gut

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Signaling Pathways in Liver Diseases Kupffer Cells

Cited by 6 publications

References 87 publications

Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis

Intraperitoneal LPS amplifies portal hypertension in rat liver fibrosis

Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

Kupffer cell activation and portal hypertension

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