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Sinusoidal endothelial liver cells in vitro release endothelin — Augmentation by transforming growth factorβ and Kupffer cell-conditioned media

Kultivierte sinusoidale Endothelzellen der Leber bilden und sezernieren Endothelin — Stimulation durch Transforming Growth Factorβ und konditionierte Kupfferzell Medien

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Summary

Endothelin is the most potent vasoconstrictor peptide known today. Using a radioimmunoassay for endothelin, we measured immunoreactive endothelin in culture media of guinea pig sinusoidal endothelial liver cells and human umbilical vein endothelial cells. A time-dependent release of immunoreactive endothelin by confluent sinusoidal endothelial liver cells in culture was found. Sinusoidal endothelial liver cells produced similar amounts of immunoreactive endothelin as umbilical vein endothelial cells, about 900 pg/μg DNA per 24 h. In the presence of transforming growth factorβ a dose-dependent increase of immunoreactive endothelin release was measured. The maximal increase of 50% was found at a concentration of 1 ng transforming growth factor per ml. To a similar extent Kupffer cell-conditioned media augmented the release of immunoreactive endothelin by sinusoidal endothelial liver cells, especially when Kupffer cells had been stimulated by endotoxin. Endotoxin itself did not alter the release of immunoreactive endothelin. Endothelin released by sinusoidal endothelial liver cells might influence the pericytes of the liver, i.e., the Ito-cells.

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Abbreviations

KC:

Kupffer cells

LSEC:

Liver sinusoidal endothelial cells

FCS:

fetal calf serum

RIA:

radioimmuno-assay

TGFβ :

transforming growth factorβ

References

  1. Adams DO (1981) Quantitation of DNA in mononuclear phagocytes. In: Adams DO, Edelson PJ, Koren HS (eds) Methods for studying mononuclear phagocytes. Academic Press, New York, pp 331–336

    Google Scholar 

  2. Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB (1987) Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci USA 84:6020–6024

    Google Scholar 

  3. Badr KF, Murray JJ, Breyer MD, Takahashi K, Inagawi T, Harris RC (1989) Mesangial cell, glomerular and renal vascular responses to endothelin in the rat kidney. J Clin Invest 83:336–342

    Google Scholar 

  4. Chandrashekhar RG, Stephenson K, Olsen MS (1990) Endothelin, a potent peptide agonist in the liver. J Biol Chem 265:17432–17435

    Google Scholar 

  5. Cotran RS, Pober JS (1989) Effects of cytokines on vascular endothelium: their role in vascular and immune injury. Kidney Int 35:969–975

    Google Scholar 

  6. De Nucci G, Thomas R, D'Orleans-Juste P, Antunes E, Walder C, Warner TD, Vane JR (1988) Pressor effects of circulating endothelin are limited by removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc Natl Acad Sci USA 85:9797–9800

    Google Scholar 

  7. Gressner AM, Bachem MG (1990) Cellular sources of non-collagenous matrix proteins: role of fat-stroing cells in fibrosis. Semin Liver Dis 10:30–46

    Google Scholar 

  8. Hexum TC, Hoeger C, Rivier JE, Bair A, Brown MR (1990) Characterization of endothelin secretion by vascular endothelial cells. Biochem Biophys Res Commun 167:294–300

    Google Scholar 

  9. Hirata Y, Yoshimi H, Takata S, Watanabe TX, Kumagaye S, Nakajiama K, Sakakibara S (1988) Cellular mechanism of action by a novel vasoconstictor endothelin in cultured rat vascular smooth muscle cells. Biochem Biophys Res Commun 154:868–875

    Google Scholar 

  10. Jaffe EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. J Clin Invest 52:2745–2756

    Google Scholar 

  11. Knook DL, Seffelaar DM, de Leeuw AM (1982) Fat-storing cells of rat liver, their isolation and purification. Exp Cell Res 139:468–471

    Google Scholar 

  12. Kurihara H, Yoshizumi M, Sugiyama T, Takaku F, Yanagisawa M, Masaki T, Hamaoki M, Kato H, Yazaki Y (1989) Transforming growth factorβ stimulates the expression of endothelin mRNA by vascular endothelial cells. Biochem Biophys Res Commun 159:1435–1440

    Google Scholar 

  13. Matsumura Y, Ikegawa R, Ohyama T, Hayashi K, Morimoto S (1989) Endothelin immunoreactivity in medium from cultured porcine aortic endothelial cells correlates with the biological activity. Biochem Biophys Res Commun 16:602–608

    Google Scholar 

  14. Nakaki T, Nakayama M, Yamamoto S, Kato R (1989) Endothelin-mediated stimulation of DNA synthesis in vascular smooth muscle cells. Biochem Biophys Res Commun 158:880–883

    Google Scholar 

  15. Nakatsukasa H, Nagy P, Evarts RP, Hsia C, Marsden E, Thorgeirsson SS (1990) Cellular distribution of transforming growth factorβ and procollagen types I, III, and IV transcripts in carbon tetrachloride-induced rat liver fibrosis. J Clin Invest 85:1833–1843

    Google Scholar 

  16. Nunez DJR, Brown MJ, Davenport AP, Neylon CB, Schofield JP, Wyse RK (1990) Endothelin-1 mRNA is widely expressed in porcine and human tissues. J Clin Invest 85:1537–1541

    Google Scholar 

  17. Ramadori G, Rieder H, Meyer zum Büschenfelde KH (1989) Gene expression of smooth muscle alpha-actin isoform in fat storing cells of rat liver identifies them as myofibroblasts. In: Wisse E, Knook DL, Decker K (eds) Cells of the hepatic sinusoid, Vol. 2. Kupffer Cell Foundation, Rijswijk Netherlands, pp 464–465

    Google Scholar 

  18. Rieder H, Ramadori G, Dienes HP, Meyer zum Büschenfelde KH (1987) Sinusoidal endothelial cells from guinea pig liver synthesize and secrete cellular fibronectin in vitro. Hepatology 7:856–864

    Google Scholar 

  19. Rieder H, Ramadori G, Allman KH, Meyer zum Büschenfelde KH (1990) Prostanoid release of cultured liver sinusoidal cells in response to endotoxin and tumor necrosis factor. Comparison with umbilical vein endothelial cells. J Hepatol 11:359–366

    Google Scholar 

  20. Schrader J, Tebbe U, Borries M, Ruschitzka F, Schoel G, Kandt M, Warneke G, Züchner C, Weber MH, Neu U, Rath W, Henning HV (1990) Plasma-endothelin bei Normalpersonen und Patienten mit nephrologisch-rheumatologischen und kardiovaskulären Erkrankungen. Klin Wochenschr 68:774–779

    Google Scholar 

  21. Serradeil-Le Gal C, Jouneaux C, Sauchez-Bueno A, Raufaste D, Roche B, Préaux AM, Maffrand JP, Cobbold PH, Hanoune J, Lotersztajn S (1991) Endothelin action in rat liver. J Clin Invest 87:133–138

    Google Scholar 

  22. Simonson MS, Dunn MJ (1990) Endothelin-1 stimulates contraction of rat glomerular mesangial cells and potentiatesβ-adrenergic-mediated cyclic adenosine monophosphate accumulation. J Clin Invest 85:790–797

    Google Scholar 

  23. Simonson MS, Wann S, Mené P, Dubyak GR, Kester M, Nakazato Y, Sedor JR, Dunn MJ (1989) Endothelin stimulates phospholipase C, Na+/H+ exchange, c-fos expression, and mitogenesis in rat mesangial cells. J Clin Invest 83:708–712

    Google Scholar 

  24. Takuwa Y, Kasaya Y, Takuwa N, Kudo M, Yanagisawa M, Goto K, Masaki T, Yamashita K (1990) Endothelin receptor is coupled to phospholipase C via a pertussis toxininsensitive guanine nucleotide-binding regulatory protein in vascular smooth muscle cells. J Clin Invest 85:653–658

    Google Scholar 

  25. Wake K (1980) Perisinusoidal stellate cells (fat storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A storing cells in extrahepatic organs. Int Rev Cytol 66:303–353

    Google Scholar 

  26. Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    Google Scholar 

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Dedicated to Professor Dr. Wolfgang Gerok on the occasion of his 65th birthday

Supported by Deutsche Forschungsgemeinschaft: grants Ri 460/1-2 and Ra 362/5-2

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Rieder, H., Ramadori, G. & Meyer zum Büschenfelde, K.H. Sinusoidal endothelial liver cells in vitro release endothelin — Augmentation by transforming growth factorβ and Kupffer cell-conditioned media. Klin Wochenschr 69, 387–391 (1991). https://doi.org/10.1007/BF01647411

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  • DOI: https://doi.org/10.1007/BF01647411

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