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MeSH Review

Kupffer Cells

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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


Chemical compound and disease context of Kupffer Cells


Biological context of Kupffer Cells


Anatomical context of Kupffer Cells


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


  1. CD18/ICAM-1-dependent oxidative NF-kappaB activation leading to nitric oxide production in rat Kupffer cells cocultured with syngeneic hepatoma cells. Kurose, I., Saito, H., Miura, S., Ebinuma, H., Higuchi, H., Watanabe, N., Zeki, S., Nakamura, T., Takaishi, M., Ishii, H. J. Clin. Invest. (1997) [Pubmed]
  2. Clearance of gut-derived endotoxins by the liver. Release and modification of 3H, 14C-lipopolysaccharide by isolated rat Kupffer cells. Fox, E.S., Thomas, P., Broitman, S.A. Gastroenterology (1989) [Pubmed]
  3. Corynebacterium parvum-elicited hepatic macrophages demonstrate enhanced respiratory burst activity compared with resident Kupffer cells in the rat. Arthur, M.J., Kowalski-Saunders, P., Wright, R. Gastroenterology (1986) [Pubmed]
  4. In vitro migratory potential of rat quiescent hepatic stellate cells and its augmentation by cell activation. Ikeda, K., Wakahara, T., Wang, Y.Q., Kadoya, H., Kawada, N., Kaneda, K. Hepatology (1999) [Pubmed]
  5. Hepatocyte transplantation activates hepatic stellate cells with beneficial modulation of cell engraftment in the rat. Benten, D., Kumaran, V., Joseph, B., Schattenberg, J., Popov, Y., Schuppan, D., Gupta, S. Hepatology (2005) [Pubmed]
  6. IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesis. Maeda, S., Kamata, H., Luo, J.L., Leffert, H., Karin, M. Cell (2005) [Pubmed]
  7. Electron microscopic evidence for an asialoglycoprotein receptor on Kupffer cells: localization of lectin-mediated endocytosis. Kolb-Bachofen, V., Schlepper-Schäfer, J., Vogell, W., Kolb, H. Cell (1982) [Pubmed]
  8. Cloning of a new cytokine that induces IFN-gamma production by T cells. Okamura, H., Tsutsi, H., Komatsu, T., Yutsudo, M., Hakura, A., Tanimoto, T., Torigoe, K., Okura, T., Nukada, Y., Hattori, K. Nature (1995) [Pubmed]
  9. Reperfusion injury after liver preservation for transplantation. Lemasters, J.J., Thurman, R.G. Annu. Rev. Pharmacol. Toxicol. (1997) [Pubmed]
  10. Glycine and uridine prevent D-galactosamine hepatotoxicity in the rat: role of Kupffer cells. Stachlewitz, R.F., Seabra, V., Bradford, B., Bradham, C.A., Rusyn, I., Germolec, D., Thurman, R.G. Hepatology (1999) [Pubmed]
  11. Quantification of sinusoidal cell function in vivo. Shiratori, Y., Tananka, M., Kawase, T., Shiina, S., Komatsu, Y., Omata, M. Semin. Liver Dis. (1993) [Pubmed]
  12. Kupffer cell activation after no-flow ischemia versus hemorrhagic shock. Jaeschke, H., Farhood, A. Free Radic. Biol. Med. (2002) [Pubmed]
  13. The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10. Dahle, M.K., Øverland, G., Myhre, A.E., Stuestøl, J.F., Hartung, T., Krohn, C.D., Mathiesen, Ø., Wang, J.E., Aasen, A.O. Infect. Immun. (2004) [Pubmed]
  14. Cell population kinetics of Kupffer cells during the onset of fibrosis in rat liver by chronic carbon tetrachloride administration. Geerts, A., Schellinck, P., Bouwens, L., Wisse, E. J. Hepatol. (1988) [Pubmed]
  15. C1 esterase inhibitor gene expression in rat Kupffer cells, peritoneal macrophages and blood monocytes: modulation by interferon gamma. Armbrust, T., Schwögler, S., Zöhrens, G., Ramadori, G. J. Exp. Med. (1993) [Pubmed]
  16. Upregulation of mouse CD14 expression in Kupffer cells by lipopolysaccharide. Matsuura, K., Ishida, T., Setoguchi, M., Higuchi, Y., Akizuki, S., Yamamoto, S. J. Exp. Med. (1994) [Pubmed]
  17. PD-1 inhibits antiviral immunity at the effector phase in the liver. Iwai, Y., Terawaki, S., Ikegawa, M., Okazaki, T., Honjo, T. J. Exp. Med. (2003) [Pubmed]
  18. The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro. Inaba, K., Witmer-Pack, M., Inaba, M., Hathcock, K.S., Sakuta, H., Azuma, M., Yagita, H., Okumura, K., Linsley, P.S., Ikehara, S., Muramatsu, S., Hodes, R.J., Steinman, R.M. J. Exp. Med. (1994) [Pubmed]
  19. Cell-specific expression of hepatocyte growth factor in liver. Upregulation in sinusoidal endothelial cells after carbon tetrachloride. Maher, J.J. J. Clin. Invest. (1993) [Pubmed]
  20. Involvement of CD95 (Apo-1/Fas) ligand expressed by rat Kupffer cells in hepatic immunoregulation. Müschen, M., Warskulat, U., Peters-Regehr, T., Bode, J.G., Kubitz, R., Häussinger, D. Gastroenterology (1999) [Pubmed]
  21. 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. Amar-Costesec, A., Prado-Figueroa, M., Beaufay, H., Nagelkerke, J.F., van Berkel, T.J. J. Cell Biol. (1985) [Pubmed]
  22. A comparison of the pharmacological properties of carbohydrate remodeled recombinant and placental-derived beta-glucocerebrosidase: implications for clinical efficacy in treatment of Gaucher disease. Friedman, B., Vaddi, K., Preston, C., Mahon, E., Cataldo, J.R., McPherson, J.M. Blood (1999) [Pubmed]
  23. Activation of interferon-gamma inducing factor mediated by interleukin-1beta converting enzyme. Gu, Y., Kuida, K., Tsutsui, H., Ku, G., Hsiao, K., Fleming, M.A., Hayashi, N., Higashino, K., Okamura, H., Nakanishi, K., Kurimoto, M., Tanimoto, T., Flavell, R.A., Sato, V., Harding, M.W., Livingston, D.J., Su, M.S. Science (1997) [Pubmed]
  24. Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells. Curran, R.D., Billiar, T.R., Stuehr, D.J., Hofmann, K., Simmons, R.L. J. Exp. Med. (1989) [Pubmed]
  25. NADPH oxidase-derived free radicals are key oxidants in alcohol-induced liver disease. Kono, H., Rusyn, I., Yin, M., Gäbele, E., Yamashina, S., Dikalova, A., Kadiiska, M.B., Connor, H.D., Mason, R.P., Segal, B.H., Bradford, B.U., Holland, S.M., Thurman, R.G. J. Clin. Invest. (2000) [Pubmed]
  26. Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene. Ling, W., Lougheed, M., Suzuki, H., Buchan, A., Kodama, T., Steinbrecher, U.P. J. Clin. Invest. (1997) [Pubmed]
  27. Cell-derived anaphylatoxins as key mediators of antibody-dependent type II autoimmunity in mice. Kumar, V., Ali, S.R., Konrad, S., Zwirner, J., Verbeek, J.S., Schmidt, R.E., Gessner, J.E. J. Clin. Invest. (2006) [Pubmed]
  28. Induction of anaphylatoxin C5a receptors in rat hepatocytes by lipopolysaccharide in vivo: mediation by interleukin-6 from Kupffer cells. Koleva, M., Schlaf, G., Landmann, R., Götze, O., Jungermann, K., Schieferdecker, H.L. Gastroenterology (2002) [Pubmed]
  29. Enhanced cyclooxygenase-2 gene expression in alcoholic liver disease in the rat. Nanji, A.A., Miao, L., Thomas, P., Rahemtulla, A., Khwaja, S., Zhao, S., Peters, D., Tahan, S.R., Dannenberg, A.J. Gastroenterology (1997) [Pubmed]
  30. Interleukin 18 together with interleukin 12 inhibits IgE production by induction of interferon-gamma production from activated B cells. Yoshimoto, T., Okamura, H., Tagawa, Y.I., Iwakura, Y., Nakanishi, K. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  31. Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4. Su, G.L., Klein, R.D., Aminlari, A., Zhang, H.Y., Steinstraesser, L., Alarcon, W.H., Remick, D.G., Wang, S.C. Hepatology (2000) [Pubmed]
  32. Induction of tumor necrosis factor alpha production by human hepatocytes in chronic viral hepatitis. González-Amaro, R., García-Monzón, C., García-Buey, L., Moreno-Otero, R., Alonso, J.L., Yagüe, E., Pivel, J.P., López-Cabrera, M., Fernández-Ruiz, E., Sánchez-Madrid, F. J. Exp. Med. (1994) [Pubmed]
  33. Heme oxygenase-1 is an antifibrogenic protein in human hepatic myofibroblasts. Li, L., Grenard, P., Nhieu, J.T., Julien, B., Mallat, A., Habib, A., Lotersztajn, S. Gastroenterology (2003) [Pubmed]
  34. New method of delivering gene-altered Kupffer cells to rat liver: studies in an ischemia-reperfusion model. Froh, M., Wheeler, M.D., Smutney, O., Zhong, Z., Bradford, B.U., Thurman, R.G. Gastroenterology (2003) [Pubmed]
  35. Increased nitric oxide synthase activity as a cause of mitochondrial dysfunction in rat hepatocytes: roles for tumor necrosis factor alpha. Kurose, I., Miura, S., Higuchi, H., Watanabe, N., Kamegaya, Y., Takaishi, M., Tomita, K., Fukumura, D., Kato, S., Ishii, H. Hepatology (1996) [Pubmed]
  36. Initiation of remote hepatic injury in the rat: interactions between Kupffer cells, tumor necrosis factor-alpha, and microvascular perfusion. Brock, R.W., Lawlor, D.K., Harris, K.A., Potter, R.F. Hepatology (1999) [Pubmed]
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