Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1961 Jan 31;113(2):437–450. doi: 10.1084/jem.113.2.437

SOME EFFECTS OF PROTEOLYTIC INHIBITORS ON TISSUE INJURY AND SYSTEMIC ANAPHYLAXIS

B W Zweifach 1, A L Nagler 1, W Troll 1
PMCID: PMC2137352  PMID: 13789017

Abstract

A study was made of the development of various forms of local and systemic injury in animals treated with inhibitors of proteolytic activity. The agents used were tosylarginine methyl ester (TAME), epsilon aminocaproic acid (EACA), and soybean trypsin inhibitor (SBTI). 1. Hemorrhagic necrosis in the skin of the rabbit following intradermal epinephrine in combination with bacterial endotoxin (either intravenous or local) was clearly suppressed by EACA, TAME, and SBTI, given systemically. Tosylarginine (TA) was ineffective. 2. No effect was observed on the classical Shwartzman reaction, the local Arthus phenomenon, or inflammation induced by xylene. 3. The lethal effects of systemic anaphylaxis in the mouse, acute endotoxemia in the rat and mouse, and drum shock in the rat are suppressed by EACA and TAME. 4. There was no effect on the generalized Shwartzman phenomenon in the rabbit and on anaphylaxis in the guinea pig. 5. The effects of EACA or TAME on the injury reactions under investigation were not due to a pharmacological or chemical action on vascular behavior per se. 6. The data provide corroborative evidence for a proteolytic step in injury phenomena which may be mediated through some common activation system. 7. The working hypothesis is advanced that local or systemic stress through the release of epinephrine may result in an increase of a circulating activator of proteolysis and that this in turn may give rise to the release of vasoactive substances,—possibly histamine, serotonin, or a polypeptide.

Full Text

The Full Text of this article is available as a PDF (755.4 KB).

Selected References

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

  1. ABLONDI F. B., HAGAN J. J., PHILIPS M., DE RENZO E. C. Inhibition of plasmin, trypsin and the streptokinase-activated fibrinolytic system by 6-aminocaproic acid. Arch Biochem Biophys. 1959 May;82(1):153–160. doi: 10.1016/0003-9861(59)90100-6. [DOI] [PubMed] [Google Scholar]
  2. ALKJAERSIG N., FLETCHER A. P., SHERRY S. xi-Aminocaproic acid: an inhibitor of plasminogen activation. J Biol Chem. 1959 Apr;234(4):832–837. [PubMed] [Google Scholar]
  3. BENNETT I. L., Jr, BEESON P. B. The effect of cortisone upon reactions of rabbits to bacterial endotoxins with particular reference to acquired resistance. Bull Johns Hopkins Hosp. 1953 Nov;93(5):290–308. [PubMed] [Google Scholar]
  4. BENNETT I. L., Jr Further investigation of effect of colloidal materials upon the Shwartzman phenomenon. Proc Soc Exp Biol Med. 1952 Oct;81(1):248–250. doi: 10.3181/00379727-81-19837. [DOI] [PubMed] [Google Scholar]
  5. BIOZZI G., BENACERRAF B., HALPERN B. N. Quantitative study of the granulopectic activity of the reticulo-endothelial system. II. A study of the kinetics of the R. E. S. in relation to the dose of carbon injected; relationship between the weight of the organs and their activity. Br J Exp Pathol. 1953 Aug;34(4):441–457. [PMC free article] [PubMed] [Google Scholar]
  6. BOVET D. Introduction to antihistamine agents and antergan derivative. Ann N Y Acad Sci. 1950 Apr 28;50(9):1089–1126. doi: 10.1111/j.1749-6632.1950.tb39905.x. [DOI] [PubMed] [Google Scholar]
  7. Beeson P. B., Technical Assistance of Elizabeth Roberts TOLERANCE TO BACTERIAL PYROGENS : II. ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM. J Exp Med. 1947 Jun 30;86(1):39–44. doi: 10.1084/jem.86.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. LANDY M., JOHNSON A. G., WEBSTER M. E., SAGIN J. F. Studies on the O antigen of Salmonella typhosa. II. Immunological properties of the purified antigen. J Immunol. 1955 Jun;74(6):466–478. [PubMed] [Google Scholar]
  9. LEVY S. W., VAILLANCOURT D. Effects of inflammation on proteins and enzymes in rat plasma. Can J Biochem Physiol. 1960 Jun;38:575–584. [PubMed] [Google Scholar]
  10. MILES A. A., WILHELM D. L. Enzyme-like globulins from serum reproducing the vascular phenomena of inflammation. I. An activable permeability factor and its inhibitor in guinea-pig serum. Br J Exp Pathol. 1955 Feb;36(1):71–81. [PMC free article] [PubMed] [Google Scholar]
  11. MILL P. J., ELDER J. M., MILES A. A., WILHELM D. L. Enzyme-like globulins from serum reproducing the vascular phenomena of inflammation. VI. Isolation and properties of permeability factor and its inhibitor in human plasma. Br J Exp Pathol. 1958 Aug;39(4):343–355. [PMC free article] [PubMed] [Google Scholar]
  12. PARRATT J. R., WEST G. B. Release of 5-hydroxytryptamine and histamine from tissues of the rat. J Physiol. 1957 Jul 11;137(2):179–192. doi: 10.1113/jphysiol.1957.sp005805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. SHERRY S., LINDEMEYER R. I., FLETCHER A. P., ALKJAERSIG N. Studies on enhanced fibrinolytic activity in man. J Clin Invest. 1959 May;38(5):810–822. doi: 10.1172/JCI103863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. STETSON C. A., Jr Studies on the mechanism of the Shwartzman phenomenon; similarities between reactions to endotoxins and certain reactions of bacterial allergy. J Exp Med. 1955 Apr 1;101(4):421–436. doi: 10.1084/jem.101.4.421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. THOMAS L. The physiological disturbances produced by endotoxins. Annu Rev Physiol. 1954;16:467–490. doi: 10.1146/annurev.ph.16.030154.002343. [DOI] [PubMed] [Google Scholar]
  16. THOMAS L. The role of epinephrine in the reactions produced by the endotoxins of gram-negative bacteria. I. Hemorrhagic necrosis produced by epinephrine in the skin of endotoxin-treated rabbits. J Exp Med. 1956 Dec 1;104(6):865–880. doi: 10.1084/jem.104.6.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. TROLL W., SHERRY S. The activation of human plasminogen by streptokinase. J Biol Chem. 1955 Apr;213(2):881–891. [PubMed] [Google Scholar]
  18. TROLL W., SHERRY S., WACHMAN J. The action of plasmin on synthetic substrates. J Biol Chem. 1954 May;208(1):85–93. [PubMed] [Google Scholar]
  19. TURPINI R., STEFANINI M. The nature and mechanism of the hemostatic breakdown in the course of experimental hemorrhagic shock. J Clin Invest. 1959 Jan 1;38(1 Pt 1):53–65. doi: 10.1172/JCI103795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. UNGAR G., HAYASHI H. Enzymatic mechanisms in allergy. Ann Allergy. 1958 Sep-Oct;16(5):542–581. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES