Abstract
Group A streptococcal pyrogenic exotoxins (SPEs) A, B, and C and alpha-amanitin enhance host susceptibility to lethal endotoxin shock. The capacity of SPE C and alpha-amanitin to prepare rabbits for the enhancement phenomenon required pretreatment of the animals 1 to 2 h before giving endotoxin. Endotoxin clearance from the circulation of rabbits pretreated with either SPE C or alpha-amanitin was reduced. Even at the time of death, significant amounts of endotoxin remained in the circulation. It is proposed that the SPE and alpha-amanitin inhibit ribonucleic acid synthesis in Kupffer cells with concomitant alteration in reticuloendothelial clearnace function, allowing endotoxin to persist in the circulation and produce host injury. All three SPE types and alpha-amanitin inhibited ribonucleic acid synthesis by 50% or greater in whole liver cells. Kupffer cells, liver cell nuclei, and liver nuclear extracts; inhibition was observed liver cells from both mice and rabbits. The inhibitory effect by SPEs was dose dependent and was observed after as little as 15 min of preincubation with liver cells. The content of ribonucleic acid in liver nuclei of mice pretreated with either SPE C or alpha-amanitan was reduced, whereas total deoxyribonucleic acid and protein content remained unaltered.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barsumian E. L., Cunningham C. M., Schlievert P. M., Watson D. W. Heterogeneity of group A streptococcal pyrogenic exotoxin type B. Infect Immun. 1978 May;20(2):512–518. doi: 10.1128/iai.20.2.512-518.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barsumian E. L., Schlievert P. M., Watson D. W. Nonspecific and specific immunological mitogenicity by group A streptococcal pyrogenic exotoxins. Infect Immun. 1978 Dec;22(3):681–688. doi: 10.1128/iai.22.3.681-688.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham C. M., Barsumian E. L., Watson D. W. Further purification of group A streptococcal pyrogenic exotoxin and characterization of the purified toxin. Infect Immun. 1976 Sep;14(3):767–775. doi: 10.1128/iai.14.3.767-775.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham C. M., Watson D. W. Alteration of clearance function by group A streptococcal pyrogenic exotoxin and its relation to suppression of the antibody response. Infect Immun. 1978 Jan;19(1):51–57. doi: 10.1128/iai.19.1.51-57.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham C. M., Watson D. W. Suppression of antibody response by group A streptococcal pyrogenic exotoxin and characterization of the cells involved. Infect Immun. 1978 Feb;19(2):470–476. doi: 10.1128/iai.19.2.470-476.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fiume L., Stirpe F. Decreased RNA content in mouse liver nuclei after intoxication with alpha-amanitin. Biochim Biophys Acta. 1966 Sep;123(3):643–645. doi: 10.1016/0005-2787(66)90239-5. [DOI] [PubMed] [Google Scholar]
- Garrity G. M., Brown A. Competition binding assay using o-methyl-[3H]-demethyl-gamma-amanitin for study of RNA polymerase B. Proc Soc Exp Biol Med. 1978 Oct;159(1):98–104. doi: 10.3181/00379727-159-40292. [DOI] [PubMed] [Google Scholar]
- Gill D. M., Meren R. ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3050–3054. doi: 10.1073/pnas.75.7.3050. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gill D. M., Pappenheimer A. M., Jr, Brown R., Kurnick J. T. Studies on the mode of action of diphtheria toxin. VII. Toxin-stimulated hydrolysis of nicotinamide adenine dinucleotide in mammalian cell extracts. J Exp Med. 1969 Jan 1;129(1):1–21. doi: 10.1084/jem.129.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HANNA E. E., WATSON D. W. HOST-PARASITE RELATIONSHIPS AMONG GROUP A STREPTOCOCCI. 3. DEPRESSION OF RETICULOENDOTHELIAL FUNCTION BY STREPTOCOCCAL PYROGENIC EXOTOXINS. J Bacteriol. 1965 Jan;89:154–158. doi: 10.1128/jb.89.1.154-158.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hale M. L., Hanna E. E. Deregulation of mouse antibody-forming cells by streptococcal pyrogenic exotoxin. II. Modification of spleen T-cell-complemented nude mouse PFC responses. Cell Immunol. 1976 Oct;26(2):168–177. doi: 10.1016/0008-8749(76)90361-0. [DOI] [PubMed] [Google Scholar]
- Hanna E. E., Watson D. W. Enhanced immune response after immunosuppression by Streptococcal pyrogenic exotoxin. Infect Immun. 1973 Jun;7(6):1009–1011. doi: 10.1128/iai.7.6.1009-1011.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iglewski B. H., Liu P. V., Kabat D. Mechanism of action of Pseudomonas aeruginosa exotoxin Aiadenosine diphosphate-ribosylation of mammalian elongation factor 2 in vitro and in vivo. Infect Immun. 1977 Jan;15(1):138–144. doi: 10.1128/iai.15.1.138-144.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacob S. T., Sajdel E. M., Munro H. N. Altered characteristics of mammalian RNA polymerase following solubilization from nuclei. Biochem Biophys Res Commun. 1968 Sep 6;32(5):831–838. doi: 10.1016/0006-291x(68)90316-1. [DOI] [PubMed] [Google Scholar]
- Kato I., Watanabe M., Kumazawa N. H. Inhibition of adenosine 3',5'-monophosphate-dependent protein kinase by staphylococcal alpha-toxin. Infect Immun. 1979 Apr;24(1):286–288. doi: 10.1128/iai.24.1.286-288.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kim Y. B., Watson D. W. Biologically active endotoxins from Salmonella mutants deficient in O- and R-polysaccharides and heptose. J Bacteriol. 1967 Nov;94(5):1320–1326. doi: 10.1128/jb.94.5.1320-1326.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levin J., Tomasulo P. A., Oser R. S. Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med. 1970 Jun;75(6):903–911. [PubMed] [Google Scholar]
- Rose W. C., Bradley S. G. Enhanced toxicity for mice of combinations of antibiotics with Escherichia coli cells or Salmonella typhosa endotoxin. Infect Immun. 1971 Nov;4(5):550–555. doi: 10.1128/iai.4.5.550-555.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SCHWAB J. H., WATSON D. W., CROMARTIE W. J. Further studies of group A streptococcal factors with lethal and cardiotoxic properties. J Infect Dis. 1955 Jan-Feb;96(1):14–18. doi: 10.1093/infdis/96.1.14. [DOI] [PubMed] [Google Scholar]
- SUGIYAMA H., MCKISSIC E. M., Jr, BERGDOLL M. S., HELLER B. ENHANCEMENT OF BACTERIAL ENDOTOXIN LETHALITY BY STAPHYLOCOCCAL ENTEROTOXIN. J Infect Dis. 1964 Apr;114:111–118. doi: 10.1093/infdis/114.2.111. [DOI] [PubMed] [Google Scholar]
- Schlievert P. M., Bettin K. M., Watson D. W. Purification and characterization of group A streptococcal pyrogenic exotoxin type C. Infect Immun. 1977 May;16(2):673–679. doi: 10.1128/iai.16.2.673-679.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlievert P. M., Schoettle D. J., Watson D. W. Nonspecific T-lymphocyte mitogenesis by pyrogenic exotoxins from group A streptococci and Staphylococcus aureus. Infect Immun. 1979 Sep;25(3):1075–1077. doi: 10.1128/iai.25.3.1075-1077.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlievert P. M., Schoettle D. J., Watson D. W. Purification and physicochemical and biological characterization of a staphylococcal pyrogenic exotoxin. Infect Immun. 1979 Mar;23(3):609–617. doi: 10.1128/iai.23.3.609-617.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlievert P. M., Watson D. W. Group A streptococcal pyrogenic exotoxin: pyrogenicity, alteration of blood-brain barrier, and separation of sites for pyrogenicity and enhancement of lethal endotoxin shock. Infect Immun. 1978 Sep;21(3):753–763. doi: 10.1128/iai.21.3.753-763.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selye H., Tuchweber B., Bertók L. Effect of lead acetate on the susceptibility of rats to bacterial endotoxins. J Bacteriol. 1966 Feb;91(2):884–890. doi: 10.1128/jb.91.2.884-890.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seyberth H. W., Schmidt-Gayk H., Hackenthal E. Toxicity, clearance and distribution of endotoxin in mice as influenced by actinomycin D, cycloheximide, -amanitin and lead acetate. Toxicon. 1972 Aug;10(5):491–500. doi: 10.1016/0041-0101(72)90175-4. [DOI] [PubMed] [Google Scholar]
- WATSON D. W. Host-parasite factors in group A streptococcal infections. Pyrogenic and other effects of immunologic distinct exotoxins related to scarlet fever toxins. J Exp Med. 1960 Feb 1;111:255–284. doi: 10.1084/jem.111.2.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Widnell C. C., Tata J. R. A procedure for the isolation of enzymically active rat-liver nuclei. Biochem J. 1964 Aug;92(2):313–317. doi: 10.1042/bj0920313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wieland T. Poisonous principles of mushrooms of the genus Amanita. Four-carbon amines acting on the central nervous system and cell-destroying cyclic peptides are produced. Science. 1968 Mar 1;159(3818):946–952. doi: 10.1126/science.159.3818.946. [DOI] [PubMed] [Google Scholar]
- Zlydaszyk J. C., Moon R. J. Fate of 51Cr-labeled lipopolysaccharide in tissue culture cells and livers of normal mice. Infect Immun. 1976 Jul;14(1):100–105. doi: 10.1128/iai.14.1.100-105.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]