Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1981 Nov;68(5):1132–1139. doi: 10.1172/JCI110357

A model of decreased functional alpha-1-proteinase inhibitor. Pulmonary pathology of dogs exposed to chloramine T.

W R Abrams, A B Cohen, V V Damiano, A Eliraz, P Kimbel, D R Meranze, G Weinbaum
PMCID: PMC370906  PMID: 6975283

Abstract

The objective of this study was to develop an animal model representative of chronic human alpha-1-proteinase inhibitor deficiency. Eight dogs were treated with a mild oxidizing agent, chloramine T, with varying regimens for 3--27 wk. The capacity of the serum to inhibit both trypsin and elastase was examined and found to respond differently. Although immunologically determined levels of protease inhibitor did not change, the ability of serum to inhibit elastase in an in vitro assay decreased in direct response to chloramine T treatment. The trypsin inhibitory capacity was less affected. Emphysemalike alterations in lung morphology were observable when histologic sections were evaluated both subjectively and objectively by mean linear intercept measurements. The data suggest that this model parallels the emphysema associated with the genetic alpha-1-proteinase inhibitor deficiency in man.

Full text

PDF
1135

Images in this article

1137Image
on p.1137
1137Image
on p.1137

Selected References

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

  1. Abrams W. R., Eliraz A., Kimbel P., Weinbaum G. The effect of the oxidizing agents chloramine-T and cigarette smoke on dog serum proteinase inhibitor(s). Exp Lung Res. 1980 Aug;1(3):211–223. doi: 10.3109/01902148009065461. [DOI] [PubMed] [Google Scholar]
  2. Abrams W. R., Kimbel P., Weinbaum G. Purification and characterization of canine alpha-1-antiproteinase. Biochemistry. 1978 Aug 22;17(17):3556–3561. doi: 10.1021/bi00610a021. [DOI] [PubMed] [Google Scholar]
  3. Bielefeld D. R., Senior R. M., Yu S. Y. A new method for determination of elastolytic activity using (14C) labeled elastin and its application to leukocytic elastase. Biochem Biophys Res Commun. 1975 Dec 15;67(4):1553–1559. doi: 10.1016/0006-291x(75)90203-x. [DOI] [PubMed] [Google Scholar]
  4. Blackwood C. E., Hosannah Y., Perman E., Keller S., Mandl I. Experimental emphysema in rats: elastolytic titer of inducing enzyme as determinant of the response. Proc Soc Exp Biol Med. 1973 Nov;144(2):450–454. doi: 10.3181/00379727-144-37610. [DOI] [PubMed] [Google Scholar]
  5. Carp H., Janoff A. Possible mechanisms of emphysema in smokers. In vitro suppression of serum elastase-inhibitory capacity by fresh cigarette smoke and its prevention by antioxidants. Am Rev Respir Dis. 1978 Sep;118(3):617–621. doi: 10.1164/arrd.1978.118.3.617. [DOI] [PubMed] [Google Scholar]
  6. Chan S. K. Alpha 1-antitrypsin in sera of inbred mice. Arch Environ Health. 1973 Oct;27(4):272–272. doi: 10.1080/00039896.1973.10666369. [DOI] [PubMed] [Google Scholar]
  7. Cohen A. B., Batra G., Petersen R., Podany J., Nguyen D. Size of the pool of alveolar neutrophils in normal rabbit lungs. J Appl Physiol Respir Environ Exerc Physiol. 1979 Aug;47(2):440–444. doi: 10.1152/jappl.1979.47.2.440. [DOI] [PubMed] [Google Scholar]
  8. Cohen A. B. Interrelationships between the human alveolar macrophage and alpha-1-antitrypsin. J Clin Invest. 1973 Nov;52(11):2793–2799. doi: 10.1172/JCI107475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cohen A. B. The effects in vivo and in vitro of oxidative damage to purified alpha1-antitrypsin and to the enzyme-inhibiting activity of plasma. Am Rev Respir Dis. 1979 Jun;119(6):953–960. doi: 10.1164/arrd.1979.119.6.953. [DOI] [PubMed] [Google Scholar]
  10. GROSS P., PFITZER E. A., TOLKER E., BABYAK M. A., KASCHAK M. EXPERIMENTAL EMPHYSEMA: ITS PRODUCTION WITH PAPAIN IN NORMAL AND SILICOTIC RATS. Arch Environ Health. 1965 Jul;11:50–58. doi: 10.1080/00039896.1965.10664169. [DOI] [PubMed] [Google Scholar]
  11. Gadek J. E., Fells G. A., Crystal R. G. Cigarette smoking induces functional antiprotease deficiency in the lower respiratory tract of humans. Science. 1979 Dec 14;206(4424):1315–1316. doi: 10.1126/science.316188. [DOI] [PubMed] [Google Scholar]
  12. Geokas M. C., Brodrick J. W., Johnson J. H., Largman C. Pancreatic elastase in human serum. Determination by radioimmunoassay. J Biol Chem. 1977 Jan 10;252(1):61–67. [PubMed] [Google Scholar]
  13. Janoff A., Carp H., Lee D. K., Drew R. T. Cigarette smoke inhalation decreases alpha 1-antitrypsin activity in rat lung. Science. 1979 Dec 14;206(4424):1313–1314. doi: 10.1126/science.316187. [DOI] [PubMed] [Google Scholar]
  14. Janoff A., Sloan B., Weinbaum G., Damiano V., Sandhaus R. A., Elias J., Kimbel P. Experimental emphysema induced with purified human neutrophil elastase: tissue localization of the instilled protease. Am Rev Respir Dis. 1977 Mar;115(3):461–478. doi: 10.1164/arrd.1977.115.3.461. [DOI] [PubMed] [Google Scholar]
  15. Johnson D., Travis J. The oxidative inactivation of human alpha-1-proteinase inhibitor. Further evidence for methionine at the reactive center. J Biol Chem. 1979 May 25;254(10):4022–4026. [PubMed] [Google Scholar]
  16. Jones E. A., Vergalla J., Steer C. J., Bradley-Moore P. R., Vierling J. M. Metabolism of intact and desialylated alpha 1-antitrypsin. Clin Sci Mol Med. 1978 Aug;55(2):139–148. doi: 10.1042/cs0550139. [DOI] [PubMed] [Google Scholar]
  17. Karlinsky J. B., Snider G. L. Animal models of emphysema. Am Rev Respir Dis. 1978 Jun;117(6):1109–1133. doi: 10.1164/arrd.1978.117.6.1109. [DOI] [PubMed] [Google Scholar]
  18. Keppler D., Lesch R., Reutter W., Decker K. Experimental hepatitis induced by D-galactosamine. Exp Mol Pathol. 1968 Oct;9(2):279–290. doi: 10.1016/0014-4800(68)90042-7. [DOI] [PubMed] [Google Scholar]
  19. Kueppers F., Bearn A. G. A possible experimental approach to the association of hereditary alpha-1-antitrypsin deficiency and pulmonary emphysema. Proc Soc Exp Biol Med. 1966 Apr;121(4):1207–1209. doi: 10.3181/00379727-121-31006. [DOI] [PubMed] [Google Scholar]
  20. Kueppers F., Fallat R. J. Alpha-1-antitrypsin deficiency: a defect in protein synthesis. Clin Chim Acta. 1969 Jun;24(3):401–403. doi: 10.1016/0009-8981(69)90111-9. [DOI] [PubMed] [Google Scholar]
  21. Kueppers F. Trypsin-inhibiting activity in sera of two strains of inbred mice. Arch Environ Health. 1977 May-Jun;32(3):108–109. doi: 10.1080/00039896.1977.10667264. [DOI] [PubMed] [Google Scholar]
  22. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  23. Makino S., Reed C. E. Distribution and elimination of exogenous alpha1-antitrypsin. J Lab Clin Med. 1970 May;75(5):742–746. [PubMed] [Google Scholar]
  24. Mass B., Ikeda T., Meranze D. R., Weinbaum G., Kimbel P. Induction of experimental emphysema. Cellular and species specificity. Am Rev Respir Dis. 1972 Sep;106(3):384–391. doi: 10.1164/arrd.1972.106.3.384. [DOI] [PubMed] [Google Scholar]
  25. Matheson N. R., Wong P. S., Travis J. Enzymatic inactivation of human alpha-1-proteinase inhibitor by neutrophil myeloperoxidase. Biochem Biophys Res Commun. 1979 May 28;88(2):402–409. doi: 10.1016/0006-291x(79)92062-x. [DOI] [PubMed] [Google Scholar]
  26. Satoh S., Kurecki T., Kress L. F., Laskowski M., Sr The dual nature of the reaction between porcine elastase and human plasma alpha1 proteinase inhibitor. Biochem Biophys Res Commun. 1979 Jan 15;86(1):130–137. doi: 10.1016/0006-291x(79)90391-7. [DOI] [PubMed] [Google Scholar]
  27. Shechter Y., Burstein Y., Patchornik A. Selective oxidation of methionine residues in proteins. Biochemistry. 1975 Oct 7;14(20):4497–4503. doi: 10.1021/bi00691a025. [DOI] [PubMed] [Google Scholar]
  28. Snider G. L., Hayes J. A., Franzblau C., Kagan H. M., Stone P. S., Korthy A. L. Relationship between elastolytic acitivity and experimental emphysema-induced properties of papain preparations. Am Rev Respir Dis. 1974 Sep;110(3):254–262. doi: 10.1164/arrd.1974.110.3.254. [DOI] [PubMed] [Google Scholar]
  29. Tuttle W. C., Jones R. K. Fluorescent antibody studies of alpha-1-antitrypsin in adult human lung. Am J Clin Pathol. 1975 Oct;64(4):477–482. doi: 10.1093/ajcp/64.4.477. [DOI] [PubMed] [Google Scholar]
  30. Weeke B. Rocket immunoelectrophoresis. Scand J Immunol Suppl. 1973;1:37–46. doi: 10.1111/j.1365-3083.1973.tb03777.x. [DOI] [PubMed] [Google Scholar]
  31. Weinbaum G., Marco V., Ikeda T., Mass B., Meranze D. R., Kimbel P. Enzymatic production of experimental emphysema in the dog. Route of exposure. Am Rev Respir Dis. 1974 Mar;109(3):351–357. doi: 10.1164/arrd.1974.109.3.351. [DOI] [PubMed] [Google Scholar]
  32. Werb Z., Gordon S. Elastase secretion by stimulated macrophages. Characterization and regulation. J Exp Med. 1975 Aug 1;142(2):361–377. doi: 10.1084/jem.142.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES