, Volume 95, Issue 1, pp 87–96 | Cite as

Caerulein-induced acute pancreatitis in rats: changes in glycoprotein-composition of subcellular membrane systems in acinar cells

  • S. Willemer
  • R. Bialek
  • H. Köhler
  • G. Adler


Caerulein-induced acute pancreatitis is characterized by the occurrence of two membrane-bound vacuolar systems in acinar cells. Beside digestive enzymes containing secretory vacuoles, lysosomal autophagic structures can be identified at the ultrastructural level. In the present study glycoconjugate patterns of the surrounding membranes were characterized by ultrastructural lectin-binding experiments using five colloidal-gold labeled lectins with distinct sugar specificities. Furthermore, the profile of membrane glycoproteins of isolated vacuolar fractions was studied by SDS-PAGE and lectin-blotting. In pancreatitis, membranes of secretory vacuoles showed a significant lower degree of lectin-binding compared to normal zymogen granules. In contrast, newly appearing autophagic vacuoles in pancreatitis revealed a strong membrane labelling for most lectins used. The pattern of membrane glycoproteins of secretory and autophagic vacuoles as determined by SDS-PAGE and lectin-blotting differed from those of normal zymogen granules resembling the protein profile of smooth microsomes. Since this pattern requires a previous passage through Golgi stacks, it is assumed that the two types of vacuoles derive from Golgi elements. For the pathogenesis of caerulein pancreatitis these vacuolar post-Golgi structures seem to play an important role.


Pancreatitis Acinar Cell Autophagic Vacuole Membrane Glycoprotein Caerulein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adler G, Hupp T, Kern HF (1979) Course and spontaneous regression of acute pancreatitis in the rat. Virchows Arch [A] 382:31–47Google Scholar
  2. Adler G, Rohr G, Kern HF (1982) Alteration in membrane fusion as a cause of acute pancreatitis in the rat. Dig Dis Sci 27:993–1002Google Scholar
  3. Adler G, Kern HF (1984) Fine structural and biochemical studies in human acute pancreatitis. In: Gyr KE, Singer MV, Sarles H (eds) Pancreatitis — Concepts and classification. Exerpta Medica, Amsterdam New York Oxford, pp 37–42Google Scholar
  4. Adler G, Hahn C, Kern HF, Rao KN (1985) Cerulein-induced pancreatitis in the rat: increased lysosomal enzyme activity and autophagocytosis. Digestion 32:10–18Google Scholar
  5. Clemente F, Meldolesi J (1975) Calcium and pancreatic secretion. I. Subcellular distribution of calcium and magnesium in the exocrine pancreas of guinea pig. J Cell Biol 65:88–102Google Scholar
  6. Dunphy WG, Rothman JE (1985) Compartmental organization of the Golgi stack. Cell 42:13–21Google Scholar
  7. Ermak TH, Rothman SS (1978) Internal organization of the zymogen granule: formation of reticular structures in vitro. J Ultrastruct Res 64:98–113Google Scholar
  8. Greenbaum LA, Hirshkowitz A (1961) Endogenous cathepsin activates trypsinogen in extracts of dog pancreas. Proc Soc Exp Biol Med 107:74–76Google Scholar
  9. Griffiths G, Brands R, Burke B, Louvard D, Warren G (1982) Viral membrane protein acquire galactose in trans Golgi cisternae during intracellular transport. J Cell Biol 95:781–792Google Scholar
  10. Griffiths G, Fuller SD, Back R, Hollinshead M, Pfeiffer S, Simons K (1989) The dynamic nature of the Golgi complex. J Cell Biol 108:277–297Google Scholar
  11. Heukeshoven J, Dernick R (1985) Simplified method for silver staining of proteins in polyacrylamide gels and the mechanism of silver staining. Electrophoresis 6:103–112Google Scholar
  12. Kassels B, Kay J (1973) Zymogens of proteolytic enzymes. Science 180:1022–1027Google Scholar
  13. Kern HF, Adler G, Scheele GA (1986) Structural and biochemical characterization of maximal and supramaximal hormonal stimulation of rat exocrine pancreas. Scand J Gastroenterol 20 [Suppl 112]:20–29Google Scholar
  14. Klausner RD (1989) Sorting and traffic in the central vacuolar system. Cell 57:703–706Google Scholar
  15. Klöppel G, Dreyer T, Willemer S, Kern HF, Adler G (1986) Human acute pancreatitis: its pathogenesis in the light of immunocytochemical and ultrastructural findings in acinar cells. Virchows Arch [A] 409:791–803Google Scholar
  16. Kyhse-Andersen J (1984) Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. J Biochem Biophys Methods 10:203–209Google Scholar
  17. Laemmli UK (1970) Cleavage of structural proteins during the assambly of the head of the bacteriophage T4. Nature 227:680–685Google Scholar
  18. Lampel M, Kern HF (1977) Acute interstitial pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch [A] 373:97–117Google Scholar
  19. Leblond CP, Bennett G (1977) Role of the Golgi apparatus in terminal glycosylation. In: Brinkley BR, Porter KR (eds) International cell biology. Rockefeller University Press, New York, pp 326–336Google Scholar
  20. Leiter EH, Dempsey EC, Eppig JJ (1977) Exocrine pancreatic insufficiency syndrome in CBA/J mice. II. Biochemical studies. Am J Pathol 86:31–46Google Scholar
  21. Lewis DS, MacDonald RJ, Kronquist KF, Ronzio RA (1977) Purification and partial characterization of an integral membrane glycoprotein from zymogen granules of dog pancreas. FEBS Lett 76:115–120Google Scholar
  22. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:263–275Google Scholar
  23. MacDonald RJ, Ronzio RA (1972) Comparative analysis of zymogen granule membrane polypeptides. Biochem Biophys Res Commun 49:377–382Google Scholar
  24. Moroi M, Jung SM (1984) Selective staining of human platelet glycoproteins using nitrocellulose transfer of electrophoresed proteins and peroxidase-conjugated lectins. Biochim Biophys Acta 798:295–301Google Scholar
  25. Pfeiffer U (1976) Lysosomen und Autophagie. Verh Dtsch Ges Pathol 60:28–64Google Scholar
  26. Ronzio RA, Kronquist KE, Lewis DS, MacDonald RJ, Mohrlock SH, O'Donnell JJ (1978) Glycoprotein synthesis in the adult pancreas. IV. Subcellular distribution of membrane glycoproteins. Biochim Biophys Acta 508:65–84Google Scholar
  27. Rothman JE (1987) Protein sorting by selective retention in the endoplasmic reticulum and Golgi stack. Cell 50:521–522Google Scholar
  28. Saito I, Hashimoto S, Saluja A, Steer ML, Meldolesi J (1987) Intracellular transport of pancreatic zymogens during caerulein supramaximal stimulation. Am J Physiol 253:G517-G526Google Scholar
  29. Saluja A, Hashimoto S, Saluja M, Powers RE, Meldolesi J, Steer ML (1987) Subcellular redistribution of lysosomal enzymes during caerulein-induced pancreatitis. Am J Physiol 253:G508-G516Google Scholar
  30. Scheele GA, Palade GE, Tartakoff AM (1978) Cell fractionation studies on the guinea pig pancreas. Redistribution of exocrine proteins during tissue homogenization. J Cell Biol 78:111–130Google Scholar
  31. Tartakoff A, Jamieson JE (1974) Fractionation of guinea pig pancreas. Methods Enzymol 31:41–59Google Scholar
  32. Tartakoff AM, Vassalli P (1983) Lectin-binding sites as markers of Golgi subcompartments: proximal-to-distal maturation of oligosaccharides. J Cell Biol 97:1243–1248Google Scholar
  33. Watanabe O, Baccino FM, Steer ML, Meldolesi J (1984) Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cells: early morphological changes during development of experimental pancreatitis. Am J Physiol 246:G457-G467Google Scholar
  34. Willemer S, Adler G (1989) Histochemical and ultrastructural characteristics of tubular complexes in human acute pancreatitis. Dig Dis Sci 34:46–51Google Scholar
  35. Willemer S, Klöppel G, Kern HF, Adler G (1989) Immunocytochemical and morphometric analysis of acinar zymogen granules in human acute pancreatitis. Virchows Archiv [A] 415:115–123Google Scholar
  36. Willemer S, Köhler H, Naumann R, Kern HF, Adler G (1990a) Glycoconjugate patterns of membranes in the pancreatic acinar cell of the rat. Histochemistry 93:319–326Google Scholar
  37. Willemer S, Bialek R, Adler G (1990b) Localization of lysosomal and digestive enzymes in cytoplasmic vacuoles in caerulein pancreatitis. Histochemistry 94:161–170Google Scholar
  38. Yamaguchi H, Kimura T, Mimura K, Nawata H (1989) Activation of proteases in cerulein-induced pancreatitis. Pancreas 4:565–571Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • S. Willemer
    • 1
  • R. Bialek
    • 2
  • H. Köhler
    • 1
  • G. Adler
    • 1
  1. 1.Department of Internal MedicinePhilipps-University MarburgMarburgFederal Republic of Germany
  2. 2.Department of PediatricsUniversity of BonnBonnFederal Republic of Germany

Personalised recommendations