Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1983 May;40(2):553–562. doi: 10.1128/iai.40.2.553-562.1983

Isolation and possible relevance of Thermoactinomyces candidus proteinases in farmer's lung disease.

R C Roberts, L P Nelles, M W Treuhaft, J J Marx Jr
PMCID: PMC264891  PMID: 6341241

Abstract

The thermophilic actinomycetes are the most common etiological agents causing hypersensitivity pneumonitis. Antigen preparations of these organisms contain proteolytic activity. Further investigation of the proteinases of the thermophilic actinomycetes was undertaken to determine whether this activity may contribute directly to the pathogenesis of hypersensitivity pneumonitis and pulmonary mycotoxicosis. The presence of proteolytic activity in aerosolized dust from moldy silage was demonstrated, and antibodies to two proteolytic enzymes from Thermoactinomyces candidus were found in the blood of farmer's lung patients who had been sensitized to this organism. These two enzymes were isolated from culture filtrate antigen preparations that had been partially characterized with respect to the proteolytic activities and their interaction with human serum proteinase inhibitors. Both proteinases belonged to the serine class of endopeptidases. Neither proteinase was inhibited by alpha 1-proteinase inhibitor or alpha 1-antichymotrypsin. Both proteinases were inhibited by alpha 2-macroglobulin. One of the proteinases had elastase activity. Inhalation of these proteinases apparently does occur, and they may induce an inflammatory response in the lungs since they are not inhibited by the main proteinase inhibitors protecting the lung.

Full text

PDF
553

Images in this article

559Image
on p.559
560Image
on p.560

Selected References

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

  1. Behnke U., Schalinatus E., Ruttloff H., Höhne W. E., Frömmel C. Charakterisierung einer Protease aus Thermoactinomyces vulgaris (Thermitase). 1. Untersuchungen zur Reinigung der Thermitase. Acta Biol Med Ger. 1978;37(8):1185–1192. [PubMed] [Google Scholar]
  2. Bell D. Y., Hook G. E. Pulmonary alveolar proteinosis: analysis of airway and alveolar proteins. Am Rev Respir Dis. 1979 Jun;119(6):979–990. doi: 10.1164/arrd.1979.119.6.979. [DOI] [PubMed] [Google Scholar]
  3. Bice D. E., McCarron K., Hoffman E. O., Salvaggio J. Adjuvant properties of Micropolyspora faeni. Int Arch Allergy Appl Immunol. 1977;55(1-6):267–274. doi: 10.1159/000231935. [DOI] [PubMed] [Google Scholar]
  4. 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. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  5. Diezel W., Kopperschläger G., Hofmann E. An improved procedure for protein staining in polyacrylamide gels with a new type of Coomassie Brilliant Blue. Anal Biochem. 1972 Aug;48(2):617–620. doi: 10.1016/0003-2697(72)90117-0. [DOI] [PubMed] [Google Scholar]
  6. Emanuel D. A., Wenzel F. J., Lawton B. R. Pulmonary mycotoxicosis. Chest. 1975 Mar;67(3):293–297. doi: 10.1378/chest.67.3.293. [DOI] [PubMed] [Google Scholar]
  7. Frömmel C., Hausdorf G., Höhne W. E., Behnke U., Ruttloff H. Charakterisierung einer Protease aus Thermoactinomyces vulgaris (Thermitase). 2. Einschritt-Feinreinigung und proteinchemische Charakterisierung. Acta Biol Med Ger. 1978;37(8):1193–1204. [PubMed] [Google Scholar]
  8. Hall P. K., Roberts R. C. Physical and chemical properties of human plasma alpha2-macroglobulin. Biochem J. 1978 Jul 1;173(1):27–38. doi: 10.1042/bj1730027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Harboe N., Ingild A. Immunization, isolation of immunoglobulins, estimation of antibody titre. Scand J Immunol Suppl. 1973;1:161–164. doi: 10.1111/j.1365-3083.1973.tb03798.x. [DOI] [PubMed] [Google Scholar]
  10. Harris J. O., Bice D., Salvaggio J. E. Cellular and humoral bronchopulmonary immune response of rabbits immunized with thermophilic actinomyces antigen. Am Rev Respir Dis. 1976 Jul;114(1):29–43. doi: 10.1164/arrd.1976.114.1.29. [DOI] [PubMed] [Google Scholar]
  11. Hunninghake G. W., Davidson J. M., Rennard S., Szapiel S., Gadek J. E., Crystal R. G. Elastin fragments attract macrophage precursors to diseased sites in pulmonary emphysema. Science. 1981 May 22;212(4497):925–927. doi: 10.1126/science.7233186. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Kuhn C., 3rd, Senior R. M. The role of elastases in the development of emphysema. Lung. 1978;155(3):185–197. [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Marx J. J., Flaherty D. K. Activation of the complement sequence by extracts of bacteria and fungi associated with hypersensitivity pneumonitis. J Allergy Clin Immunol. 1976 Apr;57(4):328–334. doi: 10.1016/0091-6749(76)90089-0. [DOI] [PubMed] [Google Scholar]
  16. Moore V. L., Hensley G. T., Fink J. N. An animal model of hypersensitivity pneumonitis in the rabbit. J Clin Invest. 1975 Oct;56(4):937–944. doi: 10.1172/JCI108173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Roberts R. C., Zais D. P., Marx J. J., Jr, Treuhaft M. W. Comparative electrophoresis of the proteins and proteases in thermophilic actinomycetes. J Lab Clin Med. 1977 Dec;90(6):1076–1085. [PubMed] [Google Scholar]
  18. Santarius K., Ryan C. Radial diffusion as a sensitive method for screening endopeptidase activity in plant extracts. Anal Biochem. 1977 Jan;77(1):1–9. doi: 10.1016/0003-2697(77)90283-4. [DOI] [PubMed] [Google Scholar]
  19. Senior R. M., Griffin G. L., Mecham R. P. Chemotactic activity of elastin-derived peptides. J Clin Invest. 1980 Oct;66(4):859–862. doi: 10.1172/JCI109926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Smith S. M., Burrell R., Snyder I. S. Complement activation by cell wall fractions of Micropolyspora faeni. Infect Immun. 1978 Nov;22(2):568–574. doi: 10.1128/iai.22.2.568-574.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith S. M., Hill J. O., Snyder I. S., Burrell R. Mitogenicity of cell wall fractions of Micropolyspora faeni. Ann Allergy. 1978 Jan;40(1):12–14. [PubMed] [Google Scholar]
  22. Treuhaft M. W., Roberts R. C., Hackbarth C., Emanuel D. A., Marx J. J., Jr Characterization of precipitin response to Micropolyspora faeni in farmer's lung disease by quantitative immunoelectrophoresis. Am Rev Respir Dis. 1979 Apr;119(4):571–578. doi: 10.1164/arrd.1979.119.4.571. [DOI] [PubMed] [Google Scholar]
  23. URIEL J. Characterization of enzymes in specific immuneprecipitates. Ann N Y Acad Sci. 1963 May 8;103:956–979. doi: 10.1111/j.1749-6632.1963.tb53748.x. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Westergaard J. L., Hackbarth C., Treuhaft M. W., Roberts R. C. Detection of proteinases in electrophoretograms of complex mixtures. J Immunol Methods. 1980;34(2):167–175. doi: 10.1016/0022-1759(80)90170-2. [DOI] [PubMed] [Google Scholar]
  26. White R., Janoff A., Godfrey H. P. Secretion of Alpha-2-macroglobulin by human alveolar macrophages. Lung. 1980;158(1):9–14. doi: 10.1007/BF02713697. [DOI] [PubMed] [Google Scholar]
  27. Yoshizawa Y., Hostetter M. W., Nakazawa T., Ripani L. M., Dawson C. A., Moore V. L. Enhancement of systemic immune response by immunization into chronically inflamed lungs. J Lab Clin Med. 1982 Jul;100(1):61–69. [PubMed] [Google Scholar]
  28. Zais D. P., Roberts R. C. System for simplified discontinuous-gradient polyacrylamide-gel electrophoresis. Clin Chem. 1977 Mar;23(3):590–592. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES