Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1970 Mar 31;131(4):745–763. doi: 10.1084/jem.131.4.745

THE TOXICITY OF STREPTOLYSIN O FOR BEATING MAMMALIAN HEART CELLS IN TISSUE CULTURE

A Thompson 1, S P Halbert 1, U Smith 1
PMCID: PMC2138779  PMID: 5430787

Abstract

Pulsating mammalian myocardial cells were found to be highly susceptible in tissue culture to rapid destruction by streptolysin O. Cessation of beating occurred almost immediately, followed within minutes by multiple cell membrane bleb formation. Parallel with these changes, the cytoplasm became intensely granular and the nuclear membrane apparently thickened when viewed by phase microscopy. At the ultrastructural level, the cell membrane blebs were found to contain relatively small numbers of granular fragments. The endoplasmic reticulum of damaged heart cells was quite swollen, and its contents were considerably condensed. The myofibers were not strikingly altered, but cytoplasmic and mitochondria vacuoles were rather abundant. Cardiac endothelial, kidney epithelial, and fibroblast cells were also susceptible to lysis by this toxin, but the reactions occurred more slowly or bleb formation was less evident. An antiserotonin drug known to be protective against streptolysin-O in vivo (UML-491), did not protect against killing of cardiac cells at the tissue culture level. Serotonin could not be detected in the culture fluid after lysis of cardiac cells by streptolysin O.

Full Text

The Full Text of this article is available as a PDF (1.8 MB).

Selected References

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

  1. BERNHEIMER A. W., CARLSON A. S., FREEMAN E. B., KELLNER A. Loss of myocardial contractility induced in isolated mammalian hearts by streptolysin O. J Exp Med. 1956 Sep 1;104(3):361–373. doi: 10.1084/jem.104.3.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BERNHEIMER A. W., SCHWARTZ L. L. EFFECT OF STAPHYLOCOCCAL AND OTHER BACTERIAL TOXINS ON PLATELETS IN VITRO. J Pathol Bacteriol. 1965 Jan;89:209–223. doi: 10.1002/path.1700890121. [DOI] [PubMed] [Google Scholar]
  3. BERNHEIMER A. W., SCHWARTZ L. L. Leucocidal agents of haemolytic streptococci. J Pathol Bacteriol. 1960 Jan;79:37–46. doi: 10.1002/path.1700790105. [DOI] [PubMed] [Google Scholar]
  4. Bernheimer A. W., Cantoni G. L. THE CARDIOTOXIC ACTION OF PREPARATIONS CONTAINING THE OXYGEN-LABILE HEMOLYSIN OF STREPTOCOCCUS PYOGENES : I. INCREASED SENSITIVITY OF THE ISOLATED FROG'S HEART TO REPEATED APPLICATION OF THE TOXIN. J Exp Med. 1945 Mar 1;81(3):295–306. doi: 10.1084/jem.81.3.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bernheimer A. W. PROPERTIES OF CERTAIN RAPIDLY ACTING BACTERIAL TOXINS AS ILLUSTRATED BY STREPTOLYSINS O AND S . Bacteriol Rev. 1948 Sep;12(3):195–202. doi: 10.1128/br.12.3.195-202.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fuve R. M., Alouf J. E., Delaunay A., Raynaud M. Cytotoxic effects in vitro of highly purified streptolysin O on mouse macrophages cultured in a serum-free medium. J Bacteriol. 1966 Oct;92(4):1150–1153. doi: 10.1128/jb.92.4.1150-1153.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GINSBURG I., GROSSOWICZ N. Effect of streptococcal haemolysins on Ehrlich ascites tumour cells. J Pathol Bacteriol. 1960 Jul;80:111–119. [PubMed] [Google Scholar]
  8. HALBERT S. P., AUERBACH T. The use of precipitin analysis in agar for the study of human streptococcal infections. IV. Further observations on the purification of group A extracellular antigens. J Exp Med. 1961 Jan 1;113:131–158. doi: 10.1084/jem.113.1.131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. HALBERT S. P., BIRCHER R., DAHLE E. Cardiac effects of streptolysin O in rabbits. Nature. 1961 Jan 21;189:232–233. doi: 10.1038/189232a0. [DOI] [PubMed] [Google Scholar]
  10. HALBERT S. P., BIRCHER R., DAHLE E. Studies on the mechanism of the lethal toxic action of streptolysin "O" and the protection by certain antiserotonin drugs. J Lab Clin Med. 1963 Mar;61:437–452. [PubMed] [Google Scholar]
  11. HALBERT S. P., BIRCHER R., DAHLE E. The analysis of streptococcal infections. V. Cardiotoxicity of streptolysin O for rabbits in vivo. J Exp Med. 1961 Apr 1;113:759–784. doi: 10.1084/jem.113.4.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HALBERT S. P. The use of precipitin analysis in agar for the study of human streptococcal infections. III. The purification of some of the antigens detected by these methods. J Exp Med. 1958 Sep 1;108(3):385–410. doi: 10.1084/jem.108.3.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HARARY I., FARLEY B. In vitro studies of single isolated beating heart cells. Science. 1960 Jun 3;131(3414):1674–1675. doi: 10.1126/science.131.3414.1674. [DOI] [PubMed] [Google Scholar]
  14. HIRSCH J. G., BERNHEIMER A. W., WEISSMANN G. MOTION PICTURE STUDY OF THE TOXIC ACTION OF STREPTOLYSINS ON LEUCOCYTES. J Exp Med. 1963 Aug 1;118:223–228. doi: 10.1084/jem.118.2.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Halpern B. N., Rahman S. Studies on the cardiotoxicity of streptolysin O. Br J Pharmacol Chemother. 1968 Mar;32(3):441–452. doi: 10.1111/j.1476-5381.1968.tb00445.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. KEISER H., WEISSMANN G., BERNHEIMER A. W. STUDIES ON LYSOSOMES. IV. SOLUBILIZATION OF ENZYMES DURING MITOCHONDRIAL SWELLING AND DISRUPTION OF LYSOSOMES BY STREPTOLYSIN S AND OTHER HEMOLYTIC AGENTS. J Cell Biol. 1964 Jul;22:101–113. doi: 10.1083/jcb.22.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lavail M. M., 3rd A method of embedding selected areas of tissue cultures for electron microscopy. Tex Rep Biol Med. 1968 Summer;26(2):215–222. [PubMed] [Google Scholar]
  18. Mark G. E., Strasser F. F. Pacemaker activity and mitosis in cultures of newborn rat heart ventricle cells. Exp Cell Res. 1966 Nov-Dec;44(2):217–233. doi: 10.1016/0014-4827(66)90427-7. [DOI] [PubMed] [Google Scholar]
  19. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. ROWEN R., BERNHEIMER A. W. The toxic action of preparations containing the oxygen-labile hemolysin of Streptococcus pyogenes. V. Mechanism of refractoriness to the lethal effect of the toxin. J Immunol. 1956 Jul;77(1):72–79. [PubMed] [Google Scholar]
  21. Reitz B. A., Prager D. J., Feigen G. A. An analysis of the toxic actions of purified streptolysin O on the isolated heart and separate cardiac tissues of the guinea pig. J Exp Med. 1968 Dec 1;128(6):1401–1424. doi: 10.1084/jem.128.6.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Taranta A. Factors influencing recurrent rheumatic fever. Annu Rev Med. 1967;18:159–172. doi: 10.1146/annurev.me.18.020167.001111. [DOI] [PubMed] [Google Scholar]
  23. ZUCKER-FRANKLIN D. ELECTRON MICROSCOPE STUDY OF THE DEGRANULATION OF POLYMORPHONUCLEAR LEUKOCYTES FOLLOWING TREATMENT WITH STREPTOLYSIN. Am J Pathol. 1965 Sep;47:419–433. [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES