Skip to main content
SpringerLink
Log in

Pancreaticobiliary Maljunction-Associated Pancreatitis: An Experimental Study on the Activation of Pancreatic Phospholipase A2

  • Original Scientific Reports
  • Published:
World Journal of Surgery Aims and scope Submit manuscript

Abstract

Congenital dilatation of the bile duct (CDBD), or choledochal cyst, is often complicated by recurrent pancreatitis. Reflux of pancreatic juice into the bile duct through pancreaticobiliary maljunction (PBM), an anomaly commonly associated with CDBD, and ensuing activation of pancreatic enzymes could be involved in the pathophysiologic mechanism of recurrent pancreatitis. A study was undertaken to follow the time course of the activity of phospholipase A2 (PLA2) in animal models of PBM. The assay procedures for PLA2 were evaluated, as were the conditions for separating the active enzyme from its inactive proenzyme (pro-PLA2) by immunoblotting. A rat model was designed according to Block’s method with some modifications. The kinetics of prophospholipase A2 (proPLA2) activation in bile was examined by measuring PLA2 activity and by immunoblotting using anti-rat pancreatic enzyme antibody after separating PLA2 from its zymogen under nonreducing conditions. Experimental animals were divided into three groups: group 1 (PBM group) in which bile and pancreatic juice were mixed with occlusion of the papilla; group 2, in which the papilla and hepatic hilus were occluded without mixing the two juices; and group 3, in which simple laparotomy was done. In group 1 animals, pro-PLA2 in bile was activated to its active form. In group 2 animals, where proPLA2 was predominant, there was only slight elevation of PLA2 activity in bile. In group 1 an immunohistologic study demonstrated localization of PLA2 around necrotic foci in the pancreatic parenchyma. These results suggest the involvement of activated PLA2 in the pathogenesis of choledochal cyst-associated pancreatitis.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Blumenstock, D.A., Mithoefer, J., Santulli, R.V.: Acute pancreatitis in children. Pediatrics 19:1002, 1957

    CAS  PubMed  Google Scholar 

  2. Gibson, L.E., Haller, J.A.: Acute pancreatitis associated with congenital cyst of the common bile duct. J. Pediatr. 55:650, 1959

    Article  CAS  PubMed  Google Scholar 

  3. Karjoo, M., Bishop, H.C., Borns, P., Holtzapple, P.G.: Choledochal cyst presenting as recurrent pancreatitis. Pediatrics 51:289, 1973

    CAS  PubMed  Google Scholar 

  4. Raffensperger, J.G., Given, G.Z., Warrner, R.A.: Fusiform dilatation of the common bile duct with pancreatitis. J. Pediatr. Surg. 8:907, 1973

    Article  CAS  PubMed  Google Scholar 

  5. Japanese Study Group on Pancreaticobiliary Maljunction: Diagnostic criteria of pancreatico-biliary maljunction. J. Hepat. Biliary Pancr. Surg. 1:219, 1994

    Article  Google Scholar 

  6. Babbitt, D.P.: Choledochal cyst: new etiological concept based on anomalous relationships of common bile duct and pancreatic bulb. Ann. Radiol. (Paris) 12:231, 1969

    CAS  Google Scholar 

  7. Okada, A., Oguchi, Y., Kamata, S., Ikeda, Y., Kawashima, Y., Saito, R.: Common channel syndrome: diagnosis with endoscopic retrograde cholangiopancreatography and surgical treatment. Surgery 93:634, 1983

    CAS  PubMed  Google Scholar 

  8. Okada, A., Nakamura, T., Higaki, J., Okumura, K., Kamata, S., Oguchi, Y.: Congenital dilatation of the bile duct in 100 instances and its relationship with anomalous junction. Surg. Gynecol. Obstet. 171:291, 1990

    CAS  PubMed  Google Scholar 

  9. Rinderknecht, H.: Activation of pancreatic zymogens: normal activation, premature intrapancreatic activation, protective mechanisms against inappropriate activation. Dig. Dis. Sci. 31:314, 1986

    Article  CAS  PubMed  Google Scholar 

  10. Nevalainen, T.J.: The role of phospholipase A in acute pancreatitis. Scand. J. Gastroenterol. 15:641, 1980

    Article  CAS  PubMed  Google Scholar 

  11. Vades, P., Pruzanski, W.: Role of secretory phospholipase Ab2 in the pathobiology of disease. Lab. Invest. 55:391, 1986

    Google Scholar 

  12. Block, M.A., Wakim, K.G., Baggenstoss, A.H.: Experimental studies concerning factors in the pathogenesis of acute pancreatitis. Surg. Gynecol. Obstet. 99:83, 1954

    CAS  PubMed  Google Scholar 

  13. Ceska, M., Birath, K., Brown, B.: A new and rapid method for the clinical determination of α-amylase activities in human serum and urine: optimal conditions. Clin. Chim. Acta 26:437, 1969

    Article  CAS  PubMed  Google Scholar 

  14. Preiser, H., Schmitz, J., Maestracci, D.: Modification of an assay for trypsin and its application for the estimation of enteropeptidase. Clin. Chim. Acta 59:169, 1975

    Article  CAS  PubMed  Google Scholar 

  15. Bradford, M.M.: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal. Biochem. 72:248, 1976

    Article  CAS  PubMed  Google Scholar 

  16. Tojo, H., Ono, T., Okamoto, M.: Spleen phospholipase Ab2. Methods Enzymol. 197:390, 1991

    CAS  PubMed  Google Scholar 

  17. Laemmli, U.K.: Cleavage of structural proteins during the assembly of the head of bacterophage Tb4. Nature 227:680, 1970

    Article  CAS  PubMed  Google Scholar 

  18. Sugano, S., Ohnishi, T., Hatae, N., et al.: Monoclonal antibodies against bovine adrenal cytochrome P-450 11β and cytochrome P-450bSCC: their isolation, characterization and application to immuno-histochemical analysis of adrenal cortex. J. Steroid Biochem. 23:1013, 1985

    Article  CAS  PubMed  Google Scholar 

  19. Ono, T., Tojo, H., Inoue, K.: Rat pancreatic phospholipase Ab2: purificaiton, characterization, and N-terminal amino acid sequence. J. Biochem. 96:785, 1972

    Google Scholar 

  20. Nakamura, T.: An experimental study on pancreatitis associated with special reference to the activation of prophospholipase Ab2 in bile. J. Jpn. Surg. Soc. [Nippon Geka Gakkai Zasshi] 95:382, 1994

    CAS  Google Scholar 

  21. Hsu, S.M., Raine, L., Fanger, H.: A comparative study of the peroxidase-antiperoxidase method and an avidin biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am. J. Clin. Pathol. 75:734, 1981

    CAS  PubMed  Google Scholar 

  22. Tojo, H., Ono, T., Kuramitsu, S., Kagamiyama, H., Okamoto, M.: A phospholipase Ab2 in the supernatant fraction of rat spleen: its similarity to rat pancreatic phospholipase Ab2. J. Biol. Chem. 263:5724, 1988

    CAS  PubMed  Google Scholar 

  23. Ohkawa, H., Sawaguchi, S., Yamazaki, Y., Sakaniwa, M., Ishikawa, A.: Research on animal models of the anomalous pancreatico-biliary ductal union. Jpn. J. Pediatr. Surg. 18:185, 1982

    Google Scholar 

  24. Pieterson, W.A., Vidal, J.C., Volwerk, J.J., deHaas, G.H.: Zymogencatalyzed hydrolysis of monomeric substrates and the presence of a recognition site for lipid-water interfaces in phospholipase Ab2. Biochemistry 13:1455, 1974

    Article  CAS  PubMed  Google Scholar 

  25. Holbling, N., EI-Kalak, H., Georgopoulos, A., Stilianu, L., Hacker, G.: Phospholipase-Ab1 and Ab2 in experimental acute pancreatitis in rats. Res. Exp. Med. 185:131, 1985

    Article  CAS  Google Scholar 

  26. Dehaas, G.H., Sanda, L., Roger, L.: Positional specific hydrolysis of phospholipids by pancreatic lipase. Biochim. Biophys. Acta 106:638, 1965

    Article  CAS  Google Scholar 

  27. Schroder, T., Kivilaakso, E., Kinnunen, P.K.J., Lempine, M.: Serum phospholipase Ab2 in human acute pancreatitis. Scand. J. Gastroenterol. 15:633, 1980

    Article  CAS  PubMed  Google Scholar 

  28. Nevalainen, T.J., Eskola, J.U., Aho, A.J., Havia, V.T., Lovqren, T.N.E., Nato, V.: Immunoreactive phospholipase Ab2 in serum in acute pancreatitis and pancreatic cancer. Clin. Chem. 31:1116, 1974

    Google Scholar 

  29. Westermarck, E., Rimaila-Parnanen, E.: Serum phospholipase Ab2 in canine acute pancreatitis. Acta Vet. Scand. 24:477, 1983

    CAS  PubMed  Google Scholar 

  30. Mizuma, K., Schroder, T., Kaarne, M., Korpela, H., Lempinen, M.: Serum phospholipase Ab2 in diet-induced pancreatitis. Eur. Surg. Res. 16:156, 1984

    Article  CAS  PubMed  Google Scholar 

  31. Grant, D.A.W., Jones, P.A., Hermon-Taylor, J.: The biliary excretion of enterokinase in rats. Biochem. J. 198:315, 1981

    CAS  PubMed  Google Scholar 

  32. Talbot, R.W., Grant, D.A.W., Hermon-Taylor, J.: Displacement of endogenous enterokinase into portal venous blood and bile following luminal perfusion of proximal small intestine in guinea pigs. Dig. Dis. Sci. 29:1009, 1984

    Article  CAS  PubMed  Google Scholar 

  33. Herriott, B.A., Palmer, A.A.: Rupture of small ducts and acini in the pancreas of the rat and guinea pig following major duct obstruction. Aust. J. Exp. Biol. Med. Sci. 44:143, 1966

    Article  CAS  PubMed  Google Scholar 

  34. Bergentz, S.E., Edlund, Y.: Cortisone in experimental acute pancreatitis lesion. Acta Chir. Scand. 119:24, 1960

    CAS  PubMed  Google Scholar 

  35. Edlund, R., Ekholm, R., Zelander, T.: The morphological basis of acute pancreatitis edema: a light and electron microscopical study on rats. Acta Chir. Scand. 123:389, 1962

    CAS  PubMed  Google Scholar 

  36. Anderson, M.C., Mehn, W.H., Method, H.L.: An evaluation of the common channel as a factor in pancreatic or biliary disease. Ann. Surg. 151:379, 1960

    Article  CAS  PubMed  Google Scholar 

  37. White, T.T., Magee, D.F.: Perfusion of the dog pancreas with bile without production of pancreatitis. Ann. Surg. 151:245, 1960

    Article  CAS  PubMed  Google Scholar 

  38. Elliott, D.W., Williams, R.D., Zollinger, R.M.: Alterations in the pancreatic resistance to bile in the pathogenesis of acute pancreatitis. Ann. Surg. 146:669, 1957

    Article  CAS  PubMed  Google Scholar 

  39. Armstrong, C.P., Taylor, T.V., Torrance, H.B.: Pressure, volume and the pancreas. Gut 26:615, 1985

    Article  CAS  PubMed  Google Scholar 

  40. Nevalainen, T.J., Aho, H.J., Eskola, J.U., Suonpaa, A.K.: Immunohistochemical localization of phospholipase Ab2 in human. Acta Pathol. Microbiol. Immunol. Scand. [A] 91:97, 1983

    CAS  Google Scholar 

  41. Aho, H.J., Sternby, B., Nevalainen, T.J.: Fat necrosis in human acute pancreatitis: an immunohistological study. Acta Pathol. Microbiol. Immunol. Scand. [A] 94:101, 1986

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatric Surgery, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565, Japan

    Tetsuro Nakamura M.D., Akira Okada M.D. & Jun Higaki M.D.

  2. Department of Molecular and Physiological Chemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565, Japan

    Hiromasa Tojo M.D. & Mitsuhiro Okamoto M.D.

Authors
  1. Tetsuro Nakamura M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akira Okada M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun Higaki M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiromasa Tojo M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mitsuhiro Okamoto M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nakamura, T., Okada, A., Higaki, J. et al. Pancreaticobiliary Maljunction-Associated Pancreatitis: An Experimental Study on the Activation of Pancreatic Phospholipase A2 . World J. Surg. 20, 543–550 (1996). https://doi.org/10.1007/s002689900084

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s002689900084

Keywords

Search

Navigation