Digestive Diseases and Sciences

, Volume 33, Issue 3, pp 282–288

Protease inhibitor and defective proteolysis in cystic fibrosis

  • Monica C. Hsieh
  • Helen K. Berry
Original Articles


Meconium specimens from 18 infants with cystic fibrosis (CF) had strong trypsin inhibitory activity (TIA). The same specimens, which contained increased quantities of undigested proteins, had normal concentrations of immunoreactive trypsin (IRT), but deficient trypsin catalytic activity (TCA). TIA was not detected in any specimen from non-CF infants who had high concentration of proteins comparable to that of CF infants. Subjecting meconium supernatant of CF infants to Sephadex G-75 gel filtration revealed that TCA was greatly enhanced in effluents after fractions were activated by porcine trypsin. TCA was present in the same fractions with IRT. The findings suggested that proteases were secreted into the intestinal lumen in CF infants prior to birth. Deficient proteolysis in the disease might be due to the presence of a trypsin inhibitor.

Key words

cystic fibrosis meconium protease inhibitor meconium immunoreactive trypsin defective proteolysis in CF 


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  1. 1.
    Green MN, Schwachman H: Presumptive tests for cystic fibrosis based on serum protein in meconium. Pediatrics 41:989–992, 1968PubMedGoogle Scholar
  2. 2.
    Hellsing K, Kollberg H: Analysis of albumin in meconium for early detection of cystic fibrosis. A methodological study. Scand J Clin Lab Invest 33:333–340, 1974PubMedGoogle Scholar
  3. 3.
    Lebenthal E: Pancreatic insufficiency in cystic fibrosis: Result of defect in ontogenesis of the exocrine pancreas. J Ped Gastroenterol Nutr 3 (Suppl 1):555–566, 1984Google Scholar
  4. 4.
    Lloyd-Still J:In Textbook of Cystic Fibrosis. J Lloyd-Still (ed). Boston, John Wright PSG, 1983, pp 19–31.Google Scholar
  5. 5.
    Berry HK, Hsieh MC: Mechanism for detective proteolysis in cystic fibrosis.In Cystic Fibrosis: Horizons. B Lawson (ed). Proceedings of the 9th International Cystic Fibrosis Congress. New York, Wiley, 1984, p 315Google Scholar
  6. 6.
    Hsieh MC, Berry HK: Meconium from infants with cystic fibrosis contains immunoreactive trypsinogen. Pediatr Res 18:200A, 1984 (abstract)Google Scholar
  7. 7.
    Berry HK, Kellogg FN, Lichstein SR, Ingberg RL: Elevated meconium lactase activity, its use as a screening test for cystic fibrosis. Am J Dis Child 134:930–934, 1982Google Scholar
  8. 8.
    Hsieh MC, Berry HK: Trypsin inhibitor in cystic fibrosis meconium. Fed Proc 43:677, 1984 (abstract)Google Scholar
  9. 9.
    Hsieh MC, Berry HK: Fluorometric meconium albumin test for cystic fibrosis (CF). Fourth National Symposium on Newborn Screening, Columbus, OH. Sept 1985 (abstract #40)Google Scholar
  10. 10.
    Gibson LE, Cooke RE: A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Pediatrics 23:545–549, 1958Google Scholar
  11. 11.
    Kirby LT, Applegarth DA, Davidson AFG, Wong LTK, Hardwick DF: Use of dried blood spot in immunoreactive trypsin assay for detection of cystic fibrosis. Clin Chem 27:678–680, 1981PubMedGoogle Scholar
  12. 12.
    Hsieh MC, Berry HK: Measurement of trypsin-like activity of saliva, serum and meconium by a synthetic substrate carbobenzoxy-l-arginine-7-amino-4-methylcoumarin amide (CAMCA). Clin Chim Acta 138:221–227, 1984PubMedGoogle Scholar
  13. 13.
    Imondi AR, Stradley P, Butler ER, Wolgemuth RL: A method for the assay of chymotrypsin in crude biological materials. Anal Biochem 54:199–204, 1973PubMedGoogle Scholar
  14. 14.
    Yamato C, Kinoshita K: A simple assay for measurement ofp-aminobenoic acid (PABA) in urine.In Pancreatic Function Diagnostant. M Masuda (ed). Tokyo, Iagaku-Shoin, 1978, pp 138–142Google Scholar
  15. 15.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951PubMedGoogle Scholar
  16. 16.
    Eddeland A, Ohlsson K: Purification and immunochemical quantitation of human pancreatic secretory trypsin inhibitor. Scand J Clin Lab Invest 38:261–267, 1978PubMedGoogle Scholar
  17. 17.
    Mancini G, Carbonara AO, Hermans JF: Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2:235–254, 1965PubMedGoogle Scholar
  18. 18.
    Kitahara T, Takatsuka Y, Fujimoto K, Tanaka S, Ogawa M, Kosaki G: Radioimmunoassay for human pancreatic secretory trypsin inhibitor: Measurement of serum pancreatic secretory trypsin inhibitor in normal subjects and subjects with pancreatic diseases. Clin Chim Acta 103:135–143, 1980PubMedGoogle Scholar
  19. 19.
    Steel RG, Torrie J: Principles and Procedures of Statistics. New York, McGraw-Hill, 1960Google Scholar
  20. 20.
    Hasdai A, Liener I: Growth, digestibility and enzymatic activities in the pancreas and intestines of hamsters fed raw and heated soy flour. J Nutr 113:662–668, 1983PubMedGoogle Scholar
  21. 21.
    Macleod E, Derbenwick JP: Comparison of pancreatic changes induced in rats by soybean and egg-white trypsin inhibitors fed with different levels of nitrogen. J Nutr 102:469–478, 1972PubMedGoogle Scholar
  22. 22.
    Fölsch UR, Creutzfeldt W: Adaptation of the pancreas during treatment with enzyme inhibitors in rat and man. Scand J Gastroenterol Suppl 112:54–63, 1985PubMedGoogle Scholar
  23. 23.
    Struthers BJ, MacDonald JR, Dahlgren RR, Hopkins DT: Effects on the monkey, pig and rat pancreas of soy products with varying levels of trypsin inhibitor and comparison with the administration of cholecystokinin. J Nutr 113:86–97, 1983PubMedGoogle Scholar
  24. 24.
    Ausman LM, Harwood JP, King NW, Sehgal PK, Nicolosi RJ, Hegsted DM, Liener IE, Dohatucci D, Tracza J: The effect of long-term soy protein and milk protein feeding on the pancreas ofCefus alfifrons monkeys. J Nutr 115:1691–1701, 1985PubMedGoogle Scholar
  25. 25.
    Temler RS, Darmond CA, Simon E, Marel B, Mettraux C: Response of rat pancreatic proteases to dietary proteins, their hydrolysates and soybean trypsin inhibitor. J Nutr 114:270–278, 1984PubMedGoogle Scholar
  26. 26.
    Greene LJ, Pubols HM, Bartelt DC: Human pancreatic secretory trypsin inhibitor. Methods Enzymol 45:813–825Google Scholar
  27. 27.
    Feinstein G, Hofstein R, Kolfman J, Sokolovsky M: Human pancreatic proteolytic enzymes and protein inhibitors. Isolation and molecular properties. Eur J Biochem 43:569–581, 1974PubMedGoogle Scholar
  28. 28.
    Kress LF, Laskowski M Sr: Purification, properties and composition of α1-trypsin inhibitor from human plasma.In Proteinase Inhibitors. Proceedings of the 2nd International Research Conference. H Fritz, H Tschesche, LJ Greene, E Truscheit (eds). New York, Springer-Verlag, 1974, pp 23–30Google Scholar
  29. 29.
    Abboud S, Neal JL: Enteropeptidase, protease and antiprotease activities in the stool of cystic fibrosis patients.In Perspectives in Cystic Fibrosis. Proceedings of the 8th International Cystic Fibrosis Congress. J Sturgess (ed). Toronto, Imperial Press, 1980, 1aGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1988

Authors and Affiliations

  • Monica C. Hsieh
    • 1
  • Helen K. Berry
    • 1
  1. 1.Children's Hospital Medical CenterCincinnati

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