Disease relevance of Kupffer Cells

• CD18/ICAM-1-dependent oxidative NF-kappaB activation leading to nitric oxide production in rat Kupffer cells cocultured with syngeneic hepatoma cells [1].
• This paper describes experiments that were designed to study postuptake modification by isolated rat Kupffer cells of a 3H,14C-biosynthetically labeled endotoxin purified from Escherichia coli J5 as assessed by cesium chloride isopyknic density gradients and gel permeation chromatography [2].
• Corynebacterium parvum-elicited hepatic macrophages demonstrated significantly enhanced superoxide production and HMPS activity compared with normal Kupffer cells, both in the absence of specific stimuli (O2-. 3.3-fold, HMPS 5.3-fold) and after exposure to phorbol myristate acetate (O2-. 4.5-fold, HMPS 5.3-fold) [3].
• These data indicate that quiescent stellate cells undergo migration, which is linked to proliferation and enhanced by PDGF/BB and Kupffer cells, suggesting the involvement of this function in the initial phase of development of postnecrotic fibrosis [4].
• Inhibition of Kupffer cells by gadolinium chloride, blockade of tumor necrosis factor alpha (TNF-alpha) activity with etanercept or attenuation of liver ischemia with nitroglycerin did not decrease this hepatic stellate cell perturbation [5].

High impact information on Kupffer Cells

• Decreased hepatocarcinogenesis was also found in mice lacking IKKbeta in both hepatocytes and hematopoietic-derived Kupffer cells [6].
• Recognition of ASF-gold by Kupffer cells is completely abolished in the presence of N-acetyl-D-galactosamine (25 mM) or EGTA (3 mM), but is not significantly reduced by N-acetyl-D-glucosamine or D-mannose (25 mM) [7].
• Electron microscopic evidence for an asialoglycoprotein receptor on Kupffer cells: localization of lectin-mediated endocytosis [7].
• Messenger RNAs for IGIF and interleukin-12 (IL-12) are readily detected in Kupffer cells and activated macrophages [8].
• Down-regulation of Kupffer cells with calcium blockers or pentoxifylline improves graft survival, whereas priming with lipopolysaccharide or alcohol worsens survival [9].

Chemical compound and disease context of Kupffer Cells

• Because bacterial endotoxin activates Kupffer cells, the purpose of this study was to clarify the role of Kupffer cells in the mechanism of D-galactosamine hepatotoxicity in rats and determine whether uridine, a compound that rescues animals from D-galactosamine toxicity, affects Kupffer cells [10].
• However, when the phagocytic function of Kupffer cells is impaired by frog virus 3 or alcohol, endothelial cells have been found to take up particles larger than 1 micron in diameter after the injection of an excess amount of latex particles [11].
• In contrast, the 10-fold increase of plasma GSSG and the 9-fold higher spontaneous superoxide formation of Kupffer cells after 60 min of hepatic no-flow ischemia followed by 90 min of reperfusion demonstrated the activation of Kupffer cells in this experimental model [12].
• Divergences in the regulatory pathways controlling TNF-alpha, IL-10, and IL-6 production in Kupffer cells following LPS or LTA stimulation may create a basis for understanding how the balance between pro- and anti-inflammatory cytokines is regulated in the liver following infections by gram-positive or gram-negative bacteria [13].
• The cell population kinetics of Kupffer cells (KCs) were investigated during the induction of fibrosis in rat liver by carbon tetrachloride [14].

Biological context of Kupffer Cells

• C1 esterase inhibitor gene expression in rat Kupffer cells, peritoneal macrophages and blood monocytes: modulation by interferon gamma [15].
• Upregulation of mouse CD14 expression in Kupffer cells by lipopolysaccharide [16].
• Liver nonparenchymal cells including sinusoidal endothelial cells and Kupffer cells constitutively expressed PD-L1 and inhibited proliferation and cell division of activated T cells expressing PD-1 [17].
• Oxidative stress indicated by dichlorofluorescein fluorescence was observed in Kupffer cells cocultured with AH70 cells [1].
• Therefore, this study suggests that CD18/ICAM-1-dependent cell-to-cell interaction with hepatoma cells causes calcium mobilization and oxidative activation of NF-kappaB, which may lead to the increased production of NO in Kupffer cells [1].

Anatomical context of Kupffer Cells

• B7-2 staining was noted on liver Kupffer cells, interstitial cells of heart and lung, and profiles in the submucosa of the esophagus [18].
• In normal liver, HGF and its mRNA were abundant in lipocytes, with smaller amounts present also in sinusoidal endothelial and Kupffer cells [19].
• Supernatants derived from 24-hour but not from 48-hour interferon gamma-treated Kupffer cells killed lymphocytes by a CD95-dependent mechanism [20].
• Analytical study of microsomes and isolated subcellular membranes from rat liver. IX. Nicotinamide adenine dinucleotide glycohydrolase: a plasma membrane enzyme prominently found in Kupffer cells [21].
• Parenchymal cells (PC), Kupffer cells (KC), and liver endothelium cells (LEC) were responsible for 75%, 22%, and 3%, respectively, of the hepatocellular uptake of rGCR and for 76%, 11%, and 12%, respectively, of the hepatocellular uptake of pGCR [22].

Associations of Kupffer Cells with chemical compounds

• Lipopolysaccharide-activated ICE-deficient (ICE-/-) Kupffer cells synthesized the IGIF precursor but failed to process it into the active form [23].
• Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells [24].
• In wild-type mice, ethanol caused severe liver injury via a mechanism involving gut-derived endotoxin, CD14 receptor, production of electron spin resonance-detectable free radicals, activation of the transcription factor NF-kappaB, and release of cytotoxic TNF-alpha from activated Kupffer cells [25].
• The sum of nitrite and nitrate levels increased in the culture medium of Kupffer cells with AH70 cells as compared with those of Kupffer cells or AH70 cells alone [1].
• Extensively oxidized LDL and LDL modified by exposure to fatty acid peroxidation products were efficient competitors for the uptake of labeled oxidized LDL by SR-AI/II-deficient Kupffer cells, while acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors [26].

Gene context of Kupffer Cells

• Upon administration of anti-erythrocyte antibodies, upregulation of activating Fcgamma receptors (FcgammaRs) on Kupffer cells, as observed in WT mice, was absent in C5aR-deficient mice, and FcgammaR-mediated in vivo erythrophagocytosis was impaired [27].
• Correspondingly, it was found that hepatocytes, in contrast to Kupffer cells, did not express C5a receptors [28].
• COX-1 mRNA was decreased in Kupffer cells in rats with the most severe liver injury [29].
• Interleukin 18 (IL-18), originally called interferon (IFN)-gamma-inducing factor, is a recently cloned cytokine of approximately 18 kDa synthesized by Kupffer cells and activated macrophages [30].
• Isolated Kupffer cells exposed to increasing concentrations of LPS (0, 1, 10 ng/mL) showed a dose-dependent increase in TNF-alpha production, which was augmented and accelerated by the presence of LBP [31].

Analytical, diagnostic and therapeutic context of Kupffer Cells

• In situ hybridization experiments using a TNF-alpha RNA probe showed a significant expression of TNF-alpha mRNA in hepatocytes, Kupffer cells, and some infiltrating mononuclear cells [32].
• RESULTS: Immunohistochemistry showed that in biopsy specimens from normal livers, HO-1 protein expression was restricted to Kupffer cells [33].
• METHODS: Optimal conditions for intravenous injection in rats were established using carbon-labeled Kupffer cells [34].
• The membrane barrier dysfunction of hepatocytes, indicated by propidium iodide staining, was also induced by a 4-hour coculture with LPS-pretreated Kupffer cells [35].
• After 1.5 hours of reperfusion, both TNF-alpha and Kupffer cells were shown to contribute to global hepatocellular injury (e.g., ALT) [36].

References