Advertisement

Virchows Archiv A

, Volume 415, Issue 2, pp 115–124 | Cite as

Immunocytochemical and morphometric analysis of acinar zymogen granules in human acute pancreatitis

  • Sebastian Willemer
  • Günter Klöppel
  • Horst F. Kern
  • Guido Adler
Article

Summary

In the present study fine structural changes of acinar zymogen granules were investigated in human acute pancreatitis. Pancreatic tissue was obtained at surgery from 6 patients, prepared for ultrastructural analysis, and stained immunocytochemically for trypsinogen. Stereological parameters of zymogen granules were evaluated. The density of the immunocytochemical labelling for trypsinogen was estimated over zymogen granules, the rough endoplasmic reticulum, Golgi apparatus and the acinar lumina. In acute pancreatitis the number of zymogen granules was diminished and their size reduced. The density of the labelling for trypsinogen was unchanged over zymogen granules but showed a significant reduction over the rough endoplasmic reticulum, Golgi apparatus, and the acinar lumina. In general the integrity of zymogen granules was well preserved. Focally degenerative changes of zymogen granules and large autophagosomes were observed. From the immunogold labelling a disturbance of enzyme synthesis and secretion was suggested. Evidence is given that a disruption of the zymogen granule membranes and a fusion with lysosomal bodies might contribute to the pathogenesis of human acute pancreatitis.

Key words

Human acute pancreatitis Zymogen granules Acinar cells Electron microscopy Immunocytochemistry Morphometry 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  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. Aho HJ, Nevalainen TJ, Haria VT, Heinomen RJ, Aho AJ (1982) Human acute pancreatitis. A light and electron microscopic study. Acta pathol microbiol immunol scand [A] 90:367–373Google Scholar
  5. Aho HJ, Putzke H-P, Nevalainen TJ, Löbel D, Pelliniemi LJ, Dummler W, Suonpää AK, Tessenow W (1983) Immunohistochemical localisation of trypsinogen and trypsin in acute and chronic pancreatitis. Digestion 27:21–28Google Scholar
  6. Becker V (1981) Acute pancreatitis: Pathological anatomy and pathogenesis. World J Surgery 5:303–313Google Scholar
  7. Bendayan M, Roth J, Perrelet A, Orci L (1980) Quantitative immunocytochemical localisation of pancreatic secretory proteins in subcellular compartments of the rat acinar cell. J Histochem Cytochem 28:149–160Google Scholar
  8. Bockman DE, Büchler M, Beger HG (1986) Ultrastructure of human acute pancreatitis. Int J Pancreatol 1:141–153Google Scholar
  9. Chiari H (1906) Über die Beziehungen zwischen dem Pankreas und der Fettgewebsnekrose. Zbl Pathol 17:798–799Google Scholar
  10. Creutzfeldt W, Schmidt H (1970) Ätiology and pathogenesis of pancreatitis (Current concepts). Scand J Gastroenterol 5 (Suppl 6):47–62Google Scholar
  11. Doerr W (1964) Pathogenese der akuten und chronischen Pankreatitis. Verh dtsch Ges inn Med 70:718–758Google Scholar
  12. Epping JJ, Leiter EH (1977) Exocrine pancreatic insufficiency syndrome in CBA/J mice. I. Ultrastructural studies. Am J Pathol 86:17–30Google Scholar
  13. Gilliland L, Steer ML (1980) Effects of ethionine on digestive enzyme synthesis and discharge by mouse pancreas. Am J Physiol 239:G418-G426Google Scholar
  14. Greenbaum LA, Hirshkowitz A (1961) Endogenous cathepsin activates trypsinogen in extracts of dog pancreas. Proc Soc Exp Biol Med 107:74–76Google Scholar
  15. Heitz PhU, Klöppel G (1984) Pathomorphology of pancreatitis- Summary. In: Gyr KE, Singer MV, Sarles H (eds) Pancreatitis- Concepts and classification. Exerpta Medica, Amsterdam New York Oxford, pp 83–85Google Scholar
  16. Helin H, Mero M, Markkula H, Helin M (1980) Pancreatic acinar ultrastructure in human acute pancreatitis. Virchows Arch [A] 387:259–270Google Scholar
  17. Horisberger M (1979) Evaluation of colloidal-gold as a cytochemical marker of transmission and scanning electron microscopy. Biol Cellul 36:253–258Google Scholar
  18. Kassels B, Kay J (1973) Zymogens of proteolytic enzymes. Science 180:1022–1027Google Scholar
  19. Klöppel G, Gerkan R, Dreyer T (1984) Pathomorphology of acute pancreatitis. Analysis of 367 autopsy cases and 3 surgical specimes. In: Gyr KE, Singer MV, Sarles H (eds) Pancreatitis- Concepts and classification. Exerpta Medica, Amsterdam New York Oxford, pp 17–23Google Scholar
  20. 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
  21. Koike H, Steer ML, Meldolesi J (1982) Pancreatic effects of ethionine. Blockade of exocytosis and appearance of crinophagy and autophagy precede cellular necrosis. Am J Physiol 242:G297-G307Google Scholar
  22. 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
  23. 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
  24. Lombardi B, Estes LW, Longnecker DS (1975) Acute hemorrhagic pancreatitis (massive necrosis) with fat necrosis induced in mice by DL-ethionine fed with a choline deficient diet. Am J Pathol 79:465–480Google Scholar
  25. Oberholzer M (1983) Morphometrie in der klinischen Pathologie. Allgemeine Grundlagen. Springer, Berlin Heidelberg New YorkGoogle Scholar
  26. Rosano EL, Stolinski C, Hughes-Jones NC (1974) An antiglobin reagent labelled with colloidal gold for use in electron microscopy. Immunochemistry 11:521–522Google Scholar
  27. Saluja A, Saito J, Saluja M, Houlihan MJ, Powers RE, Meldolesi J, Steer M (1985) In vivo rat pancreatic acinar cell function during supramaximal stimulation with caerulein. Am J Physiol 249:G702-G710Google Scholar
  28. 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
  29. 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
  30. Scheele G, Adler G, Kern HF (1987) Exocytosis occurs at the lateral plasma membrane of the pancreatic acinar cell during supramaximal secretagogue stimulation. Gastroenterology 92:345–353Google Scholar
  31. Taura S, Tsunoda T, Yoshimo R (1975) Ultrastructural studies of human acute pancreatitis. Gastroent Jpn 10:132–140Google Scholar
  32. 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
  33. Weibel ER (1979) Stereological methods. Vol 1: Practical methods for biological morphometry. Academic Press, London New York Toronto Sydney San FranciscoGoogle 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

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Sebastian Willemer
    • 1
  • Günter Klöppel
    • 3
  • Horst F. Kern
    • 2
  • Guido Adler
    • 1
  1. 1.Department of Internal MedicinePhilipps-University MarburgMarburgFederal Republic of Germany
  2. 2.Department of Cell BiologyPhilipps-University MarburgMarburgFederal Republic of Germany
  3. 3.Department of PathologyFree University of BrusselsBelgium

Personalised recommendations