Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Morphological alterations and functional changes of interhepatocellular junctions induced by bile duct ligation

  • 64 Accesses

  • 71 Citations

Summary

The effect of bile duct ligation on the intercellular junctions of hepatocytes was investigated. The features and the arrangement of the bile canaliculi and the zonulae occludentes alter concomitant to the increase of the intracanalicular pressure. The lumen of the bile canaliculi enlarges and the microvilli disappear. The array of the zonulae occludentes becomes irregularly shaped, the number of strands diminishes and interruptions of the strands occur. With peroxidase a leakage in the bile-blood barrier is detected. Furthermore a disappearance of gap junctions between the hepatocytes after bile duct ligation is observed. The present investigation shows that the zonulae occludentes are mobile structures which are changed by increased unilateral pressure. Due to their ultrastructural alterations, a leakage of the permeability barrier between physiological compartments is found.

We acknowledge the helpful criticism and discussion of Prof. H.D. Fahimi. We are indebted to Mrs. B. Brühl, M. Bürkle and Ch. Walenta for technical assistance, and to stud. med. Jon Greenberg for preparing the manuscript

This is a preview of subscription content, log in to check access.

References

  1. Aoki, A., Metz, J., Forssmann, W.G.: Fixation of the rat placenta by perfusion of the maternal and fetal blood vessels. Anat. Rec. (submitted)

  2. Barr, L., Dewey, M.M., Berger, W.: Propagation of action potentials and the structure of the nexus in cardiac musle. J. gen. Physiol. 48, 797–824 (1965)

  3. Bulger, R.E., Lorentz, W.B., Colindres, R.E., Gottschalk, C.W.: Morphologic changes in rat renal proximal tubules and their tight junctions with increased intraluminal pressure. Lab. Invest. 30, 136–144 (1974)

  4. Chalcroft, J.P., Bullivant, S.: An interpretation of liver cell membrane and junction structure based on observation of freeze-fracture replicas of both sides of the fracture. J. Cell Biol. 47, 49–60 (1970)

  5. Claude, P., Goodenough, D.: Fracture faces of zonulae occludentes from “tight” and “leaky” epithelia. J. Cell Biol. 58, 390–400 (1973)

  6. De Vos, R., De Wolf-Peeters, C., Desmet, V., Bianchi, L., Rohr, H.P.: Significance of liver canalicular changes after experimental bile and ligation. Exp. molec. Path. 23, 12–34 (1975)

  7. Dreifuss, J.J., Girardier, L., Forssmann, W.G.: Etude de la propagation de l'excitation dans la ventricule de rat au moyen de solution hypertoniques. Pflügers Arch. ges. Physiol. 292, 13–33 (1966)

  8. Evan, A.P., Baker, J.T., Bengele, H.H.: Zonulae occludentes of the rat nephron under conditions of experimental expansion of blood and for fluid volume. Anat. Rec. 186, 139–150 (1976)

  9. Fahimi, H.D.: Fine structural localization of peroxidatic activity of catalase. In: Techniques of biochemical and biophysical morphology (D. Click and R. Rosenbaum, eds.), Vol. 2, p. 198. New York: John Wiley and Sons, Inc. Publishers 1975

  10. Fahimi, H.D., Karnovsky, M.J.: Fine structural localisation of exogenous peroxidase in rat liver. In: Third International Congress of Histochemistry and Cytochemistry, Summary Reports (R.M. Rosenbaum, ed.), Inc. 55 (abstr.). Berlin-Heidelberg-New York: Springer 1968

  11. Farquhar, M., Palade, G.: Junctional complexes in various epithelia. J. Cell Biol. 17, 375–412 (1963)

  12. Forssmann, W.G.: A method for in vivo diffusion tracer studies combining perfusion fixation with intravenous tracer injection. Histochemie 20, 277–286 (1969)

  13. Forssmann, W.G., Ito, S., Weihe, E., Aoki, A, Dym, M., Fawcett, D.W.: An improved perfusion fixation method for the male genital tract Anat Rec. (in press)

  14. Forssmann, W.G., Matter, A., Rouiller, Ch., Westphal, U.: Le problème des communications entre l'espace de Disse et les canalicules biliaires. Acta anat. (Basel) 65, 614 (1966)

  15. Friend, D.D., Gilula, N.B.: Variations in tight and gap junctions in mammalian tissues. J. Cell Biol. 53, 758–776 (1972)

  16. Gilula, N.B., Reeves, O.R., Steinbach, A: Metabolic coupling, ionic coupling and cell contacts. Nature (Lond.) 235, 262–265 (1972)

  17. Goodenough, D.A., Gilula, N.B.: The splitting of hepatocyte gap junctions and zonulae occludentes with hypertonic disaccharides. J. Cell Biol. 61, 575–590 (1974)

  18. Goodenough, D.A., Revel, J.P.: The permeability of isolated and in situ mouse hepatic gap junctions studied with enzymatic tracers. J. Cell Biol. 50, 81–91 (1971)

  19. Graham, R.C., Karnovsky, M.J.: The early stages of injected horseradish peroxidase in the proximal tubules of the mouse kidney: ultrastructural cytochemistry by a new technique. J. Histochem. Cytochem. 14, 291–302 (1966)

  20. Hull, B.E., Staehelin, L.A.: Functional significance of the variations in the geometrical organization of tight junction networks. J. Cell Biol. 68, 688–704 (1976)

  21. Karnovsky, M.J.: A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron microscopy. J. Cell Biol. 27, 137 (abstr.) (1965)

  22. Kreutziger, G.O.: Freeze-etching of intercellular junctions of mouse liver. Proceedings of the 26 Annual Meeting Electron Microscopy Society of America, 234–235 (1968)

  23. Loewenstein, W.R.: Permeability of membrane junctions. Ann. N.Y. Acad. Sci. 137, 441–484 (1966)

  24. Matter, A., Orci, L., Rouiller, C.: A study on the permeability barriers between Disse space and the bile canaliculus. J. Ultrastruct. Res., Suppl. 11 (1969)

  25. McNutt, N.S., Hershberg, R.A., Weinstein, R.S.: Further observations on the occurrence of nexuses in benign and malignant human cervical epithelium. J. Cell Biol. 51, 805–825 (1971)

  26. Metz, J., Forssmann, W.G., Ito, S.: Exocrine pancreas under experimental conditions. III. Membrane and cell junctions in isolated acinar cells. Cell Tiss. Res. 177, 459–474 (1977)

  27. Metz, J., Gruner, Ch., Botz, E.: Improvements in freeze-etching and freeze-fracturing. (In press)

  28. Montesano, R., Gabbiani, G., Perrelet, A., Orci, L.: in vivo induction of tight junction. Proliferation in rat liver. J. Cell Biol. 68, 793–798 (1976)

  29. Orci, L., Matter, A., Rouiller, C.: A comparative study of freeze-etch replicas and thin sections of rat liver. J. Ultrastruct. Res. 35, 1–19 (1971)

  30. Pitelka, D.R., Hamamoto, S.T., Duafala, J.G., Nemanic, M.K.: Cell contacts in the mouse mammary gland. I. Normal gland in postnatal development and the secretory cycle. J. Cell Biol. 56, 797–818 (1973)

  31. Popper, H., Schaffner, F.: Progress in liver diseases. Vol. IV. New York: Grune and Stratton 1972

  32. Rapoport, S.I., Thompson, H.K.: Osmotic opening of the blood brain barrier in the monkey without associated neurological deficits. Science (Wash. D.C.) 180, 971–973 (1973)

  33. Rösinger, B., Schiller, G, Taugner, R.: Freeze fracture study on the tight junction morphology of pars convoluta and pars recta of the renal proximal tubules. Cell Tiss. Res. (in press)

  34. Schaffner, F., Popper, M.: Morphologic studies of cholestasis. Gastroenterology 37, 565–573 (1959)

  35. Spycher, M.A.: Intercellular adhesions. An electron microscope study on freeze-etched rat hepatocytes. Z. Zellforsch. 111, 64–74 (1970)

  36. Steiner, J.W., Carruthers, J.S.: Studies on the fine structure of the terminal branches of the biliary tree: II. Observations of pathologically altered bile canaliculi. Amer. J. Path. 39, 41–58 (1961)

  37. Vial, J.D., Simon, F.R., Mackinnon, A.M.: Effect of bile duct ligation on the ultrastructural morphology of hepatocytes. Gastroenterology 70, 85–92 (1976)

  38. Wade, J.D., Karnovsky, M.J.: Fracture faces of osmotically disrupted zonulae occludentes. J. Cell Biol. 62, 344–350 (1974)

Download references

Author information

Correspondence to Priv. Doz. Dr. J. Metz III.

Additional information

Supported by the Deutsche Forschungsgemeinschaft

Research Professor of the Alexander von Humboldt-Stiftung

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Metz, J., Aoki, A., Merlo, M. et al. Morphological alterations and functional changes of interhepatocellular junctions induced by bile duct ligation. Cell Tissue Res. 182, 299–310 (1977). https://doi.org/10.1007/BF00219766

Download citation

Key words

  • Liver
  • Bile duct ligation (rat)
  • Cell membrane
  • Intercellular junctions
  • Ultrastructure
  • Freeze-fracturing