Receptor-Mediated Transfer of Proteins from Blood to Bile

  • Richard H. Hinton
  • Diane Benford
  • Lynne J. Shaw
  • Barbara M. Mullock
Part of the Methodological Surveys in Biochemistry and Analysis book series (MSBA, volume 13)


Bile proteins derive from several different sources. Firstly there is a small, mol. wt.-dependent, leakage of proteins across the tight junctions between liver cells. Secondly, proteins are solubilized from the bile-canalicular face of hepatocytes and from the luminal face of bile-duct lining cells. Thirdly there is discharge of the contents of lysosomes into bile. Finally there is selective transport of proteins across hepatocytes from blood to bile, the mechanism of which we have established by methods described in this article.

Firstly we consider how we identified which proteins are actively transported from blood to bile. In rats three proteins are thus transported: IgA, haemoglobin (in the form of hapto-globin: haemoglobin complexes) and an unidentified protein. Then we consider methods used to identify the receptors for these proteins; we have identified the receptor for IgA transport but not that for haemoglobin. Finally we describe how we investi-gated the mechanism by which the proteins move across the cell. This involves endocytosis into specialized vesicles which do not fuse with lysosomes but which follow a route across the cell very similar to that taken by proteins destined for lysosomal digestion; they are taken up from the sinusoidal face into small vesicles which move rapidly to the vicinity of the Golgi apparatus (G.a.) and then discharge into the bile canaliculus.


Tight Junction Perfuse Liver Bile Canaliculus Secretory Component Bromphenol Blue 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mullock, B.M., Dobrota, M. & Hinton, R.H. (1978) Biochim. Biophys. Acta 453, 497–507.CrossRefGoogle Scholar
  2. 2.
    Orlans, E., Peppard, J., Fitzharris, B., Payne, A, Mullock, B.M., Hinton, R.H. & Hall, J. (1983) Ann. N.Y. Acad. Sci., in press.Google Scholar
  3. 3.
    Axelsen, N.H., Kroll, J. & Weeke, B. (1973) A Manual of Quantitative Immuno-electrophoresis, Universitetforlaget, Oslo.Google Scholar
  4. 4.
    Mullock, B.M., Issa, F.S. & Hinton, R.H. (1977) Clin. Chim. Acta 79, 129–140.CrossRefGoogle Scholar
  5. 5.
    Maizel, J. (1971) Meths. Virol. 5, 179–246.Google Scholar
  6. 6.
    Higa, Y., Oshiro, S., Kino, K., Tsunoo, H. & Nakiyima, H. (1981) J. Biol. Chem. 256, 12322–12328.Google Scholar
  7. 7.
    Orlans, E., Peppard, J., Fry, J.R., Hinton, R.H. & Mullock, B.M. (1980) J. Exp. Med. 150, 1577–1581.CrossRefGoogle Scholar
  8. 8.
    Tornasi, T.B. (1970) Ann. Rev. Med. 21, 281–298.CrossRefGoogle Scholar
  9. 9.
    Orlans, E., Peppard, J., Reynolds, J. & Hall, J. (1978) J.Exp. Med. 349, 588–592.CrossRefGoogle Scholar
  10. 10.
    Hinton, R.H., Dobrota, M. & Mullock, B.M. (1980) FEBS Lett. 112, 247–250.CrossRefGoogle Scholar
  11. 11.
    Dive, C. & Heremans, I.F. (1974) Eur. J. Clin. Invest, 4, 235–239.Google Scholar
  12. 12.
    Smith, R.L. (1973) The Excretory Function of Bile, Chapman & Hall, London, 394 pp.Google Scholar
  13. 13.
    Reid, E., ed, (1.979) Cell Populations [Vol. 8, this series], Horwood, Chichester, 240 pp.Google Scholar
  14. 14.
    Reid, E., Cook, G.M.W. & Morré, D.J. (1981) Cancer- Cell Organelles [Vol. 11, this series], Horwood, Chichester, 415 pp.Google Scholar
  15. 15.
    Giblett, E. (1974) in Structure and Function of Plasma Proteins (Alison, A.C., ed.), Vol. 1, Plenum Press, London & New York, pp. 55–72.CrossRefGoogle Scholar
  16. 16.
    Wisher, M.H. & Evans, W.H. (1975) Biochem. J. 146, 375–388.Google Scholar
  17. 17.
    Graham, J.G. (1983) in Iodinated Density Gradient Media — A Practical Approach (Rickwood, D., ed.), IRL, Oxford, in press.Google Scholar
  18. 18.
    Mullock, B.M. & Hinton, R.H. (1983) Eur.J. Cell Biol. Suppl. 1, 31.Google Scholar
  19. 19.
    Birbeck, M.S.C., Cartright, C.P., Hall, J.G., Orlans, F. & Peppard, J. (1979) Immunology 37, 477–484.Google Scholar
  20. 20.
    Schwartz, A.L., Marshak-Rothstein, A., Ray, P. & Lodish, H.F. (1981) Proc. Nat. Acad. Sci. 78, 3348–3352.CrossRefGoogle Scholar
  21. 21.
    Neufeld, E.F., Sando, G.N., Garren, A.J. & Rome, L.N. (1977) J. Supramol. Struct. 6, 95–101.CrossRefGoogle Scholar
  22. 22.
    Oates, P.J. & Touster, O. (1980) J. Cell Biol. 85, 804–810.CrossRefGoogle Scholar
  23. 23.
    Schwartz, J.H. (1979) Ann. Rev. Neurosci. 2, 467–504.CrossRefGoogle Scholar
  24. 24.
    Mullock, B.M., Jones, R.S., Peppard, J. & Hinton, R.H. (1980) FEBS Lett. 120, 278–282.CrossRefGoogle Scholar
  25. 25.
    Brady, C.T., Crothen, S.D., Nasal, C. & McClave, W.O. (1980) Proc. Nat. Acad. Sci. 77, 5909–5913.CrossRefGoogle Scholar
  26. 26.
    Grant, D.A.W., Jones, P.A. & Heron-Taylor, J. (1981) Biochem. J. 198, 315–319.Google Scholar
  27. 27.
    Godfrey, P.P., Warner, M.J. & Coleman, R. (1981) Biochem. J. 136, 11–16.Google Scholar
  28. 28.
    Slot, J.W., Peppard, J. & Geuze, H.J. (1983) Abstracts, Br. Soc. Cell Biol. Mtg., Liverpool. Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Richard H. Hinton
    • 1
  • Diane Benford
    • 1
  • Lynne J. Shaw
    • 1
  • Barbara M. Mullock
    • 1
  1. 1.Robens Institute of Industrial and Environmental Health and SafetyUniversity of SurreyGuildfordUK

Personalised recommendations