Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1981 Oct;105(1):31–39.

Immunoreactive forms of cationic trypsin in plasma and ascitic fluid of dogs in experimental pancreatitis.

M C Geokas, C Largman, P R Durie, J W Brodrick, S B Ray, M O'Rourke, J Vollmer
PMCID: PMC1903870  PMID: 6170231

Abstract

A canine model of bile-induced pancreatitis has been employed to investigate time-dependent changes in the molecular forms of trypsin in blood and ascitic fluid in this disease. The distribution of immunoreactive trypsin as trypsinogen and trypsin bound to plasma inhibitors in ascitic fluid and plasma during the course of the disease has been investigated by means of a radioimmunoassay for canine pancreatic cationic trypsin. In addition, trypsinlike amidase activity was determined in plasma and ascitic fluid using Z-Gly-Gly-Arg-beta-Nap as substrate. Early plasma and ascitic fluid samples in four dogs that died contained primarily trypsinogen, while extensive activation of trypsinogen to alpha 2-macroglobulin and alpha 1-protease inhibitor-bound trypsin occurred in the course of the disease. A fifth dog survived and showed little activation of trypsinogen. In the four dogs that died, the levels of trypsinlike amidase activity in the ascitic fluid were substantial throughout the course of the disease. The plasma levels of trypsinlike activity in these animals were much lower, but increased during the disease process. The dog that survived had lower concentrations of trypsinlike activity in ascitic fluid and plasma. These results suggest that activation of trypsinogen resulting in inhibitor-bound forms of trypsin in ascitic fluid and plasma is important in the pathogenesis of acute pancreatitis.

Full text

PDF
31

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auslander M. O., Janowitz H. D. Drug therapy of acute pancreatitis. Clin Gastroenterol. 1979 Jan;8(1):219–227. [PubMed] [Google Scholar]
  2. Balldin G., Ohlsson K. Trasylol prevents trypsin-induced shock in dogs. Hoppe Seylers Z Physiol Chem. 1979 May;360(5):651–656. doi: 10.1515/bchm2.1979.360.1.651. [DOI] [PubMed] [Google Scholar]
  3. Brodrick J. W., Geokas M. C., Largman C., Fassett M., Johnson J. H. Molecular forms of immunoreactive pancreatic cationic trypsin in pancreatitis patient sera. Am J Physiol. 1979 Nov;237(5):E474–E480. doi: 10.1152/ajpendo.1979.237.5.E474. [DOI] [PubMed] [Google Scholar]
  4. Farrell P., Fitzgerald P., Fitzgerald O., McGeeney K., Geoghegan C., Heffernan A. Shock in acute pancreatitis and hypovolaemia. Gut. 1972 Oct;13(10):844–844. [PubMed] [Google Scholar]
  5. Feinstein G., Hofstein R., Koifmann J., Sokolovsky M. Human pancreatic proteolytic enzymes and protein inhibitors. Isolation and molecular properties. Eur J Biochem. 1974 Apr 16;43(3):569–581. doi: 10.1111/j.1432-1033.1974.tb03444.x. [DOI] [PubMed] [Google Scholar]
  6. Geokas M. C., Largman C., Brodrick J. W., Johnson J. H. Determination of human pancreatic cationic trypsinogen in serum by radioimmunoassay. Am J Physiol. 1979 Jan;236(1):E77–E83. doi: 10.1152/ajpendo.1979.236.1.E77. [DOI] [PubMed] [Google Scholar]
  7. Geokas M. C., Murphy R., McKenna R. D. The role of elastase in acute pancreatitis. I. Intrapancreatic elastolytic activity in bile-induced acute pancreatitis in dogs. Arch Pathol. 1968 Aug;86(2):117–126. [PubMed] [Google Scholar]
  8. Geratz J. D. Failure of a potent trypsin inhibitor to modify experimental pancreatitis in dogs: p-aminobenzamidine. Arch Surg. 1968 Mar;96(3):450–457. doi: 10.1001/archsurg.1968.01330210128026. [DOI] [PubMed] [Google Scholar]
  9. Goldstein D. A., Llach F., Massry S. G. Acute renal failure in patients with acute pancreatitis. Arch Intern Med. 1976 Dec;136(12):1363–1365. [PubMed] [Google Scholar]
  10. Harpel P. C., Mosesson M. W. Degradation of human fibrinogen by plasms alpha2-macroglobulin-enzyme complexes. J Clin Invest. 1973 Sep;52(9):2175–2184. doi: 10.1172/JCI107402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Imrie C. W., Benjamin I. S., Ferguson J. C., McKay A. J., Mackenzie I., O'Neill J., Blumgart L. H. A single-centre double-blind trial of Trasylol therapy in primary acute pancreatitis. Br J Surg. 1978 May;65(5):337–341. doi: 10.1002/bjs.1800650514. [DOI] [PubMed] [Google Scholar]
  12. Interiano B., Stuard I. D., Hyde R. W. Acute respiratory distress syndrome in pancreatitis. Ann Intern Med. 1972 Dec;77(6):923–926. doi: 10.7326/0003-4819-77-6-923. [DOI] [PubMed] [Google Scholar]
  13. KELLY T. R., BRATCHER E. P., FALOR W. H. TRYPSIN INHIBITOR IN ACUTE HEMORRHAGIC PANCREATITIS IN DOGS; EFFECT. Arch Surg. 1964 Aug;89:317–321. doi: 10.1001/archsurg.1964.01320020081013. [DOI] [PubMed] [Google Scholar]
  14. Kwaan H. C., Anderson M. C., Gramatica L. A study of pancreatic enzymes as a factor in the pathogenesis of disseminated intravascular coagulation during acute pancreatitis. Surgery. 1971 May;69(5):663–672. [PubMed] [Google Scholar]
  15. Largman C., Brodrick J. W., Geokas M. C. Purification and characterization of two human pancreatic elastases. Biochemistry. 1976 Jun 1;15(11):2491–2500. doi: 10.1021/bi00656a036. [DOI] [PubMed] [Google Scholar]
  16. Largman C., Johnson J. H., Brodrick J. W., Geokas M. C. Proinsulin conversion to desalanyl insulin by alpha2-macroglobin-bound trypsin. Nature. 1977 Sep 8;269(5624):168–170. doi: 10.1038/269168a0. [DOI] [PubMed] [Google Scholar]
  17. Ohlsson K. Comparison of affinity of trypsin for two -macroglobulin fractions and for 1 -antitrypsin in dog serum. Clin Chim Acta. 1971 Apr;32(2):215–220. doi: 10.1016/0009-8981(71)90335-4. [DOI] [PubMed] [Google Scholar]
  18. Ohlsson K. Elimination of 125-I-trypsin alpha-macroglobulin complexes from blood by reticuloendothelial cells in dogs. Acta Physiol Scand. 1971 Feb;81(2):269–272. doi: 10.1111/j.1748-1716.1971.tb04900.x. [DOI] [PubMed] [Google Scholar]
  19. Ohlsson K., Ganrot P. O., Laurell C. B. In vivo interaction beween trypsin and some plasma proteins in relation to tolerance to intravenous infusion of trypsin in dog. Acta Chir Scand. 1971;137(2):113–121. [PubMed] [Google Scholar]
  20. Ohlsson K., Tegner H. Experimental pancreatitis in the dog. Demonstration of trypsin in ascitic fluid, lymph and plasma. Scand J Gastroenterol. 1973;8(2):129–133. [PubMed] [Google Scholar]
  21. Satake K., Rozmanith J. S., Appert H. E., Carballo J., Howard J. M. Hypotension and release of kinin-forming enzyme into ascitic fluid exudate during experimental pancreatitis in dogs. Ann Surg. 1973 Apr;177(4):497–502. doi: 10.1097/00000658-197304000-00019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Thompson A. G. Proteinase inhibitors in experimental and clinical pancreatitis. Ann N Y Acad Sci. 1968 Jun 28;146(2):540–547. doi: 10.1111/j.1749-6632.1968.tb20313.x. [DOI] [PubMed] [Google Scholar]
  23. Thompson A. G. Proteinase inhibitors in experimental and clinical pancreatitis. Ann N Y Acad Sci. 1968 Jun 28;146(2):540–547. doi: 10.1111/j.1749-6632.1968.tb20313.x. [DOI] [PubMed] [Google Scholar]
  24. Worthington K. J., Cuschieri A. Estimation of plasma esterolytic activity and its in vitro inhibition by proteinase inhibitors during acute pancreatitis in the human. Br J Exp Pathol. 1976 Apr;57(2):165–169. [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES