Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1993 Sep;61(9):3988–3993. doi: 10.1128/iai.61.9.3988-3993.1993

Clostridium difficile toxin A elicits Ca(2+)-independent cytotoxic effects in cultured normal rat intestinal crypt cells.

C Fiorentini 1, G Donelli 1, P Nicotera 1, M Thelestam 1
PMCID: PMC281105  PMID: 8359922

Abstract

In rat intestinal crypt cells, Clostridium difficile toxin A induces (i) early cytoskeletal alterations involving the whole population and (ii) late effects in 30 to 40% of the cells, consisting mainly of surface blebbing and nuclear fragmentation. All these effects were Ca2+ independent and were not abolished by protein synthesis inhibitors.

Full text

PDF
3988

Images in this article

3989Image
on p.3989
3990Image
on p.3990

Selected References

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

  1. Andersson K. E., Högestätt E. D. On the mechanism of action of calcium antagonists. Acta Med Scand Suppl. 1984;681:11–24. doi: 10.1111/j.0954-6820.1984.tb08672.x. [DOI] [PubMed] [Google Scholar]
  2. Bøe R., Gjertsen B. T., Vintermyr O. K., Houge G., Lanotte M., Døskeland S. O. The protein phosphatase inhibitor okadaic acid induces morphological changes typical of apoptosis in mammalian cells. Exp Cell Res. 1991 Jul;195(1):237–246. doi: 10.1016/0014-4827(91)90523-w. [DOI] [PubMed] [Google Scholar]
  3. Caspar M., Florin I., Thelestam M. Calcium and calmodulin in cellular intoxication with Clostridium difficile toxin B. J Cell Physiol. 1987 Jul;132(1):168–172. doi: 10.1002/jcp.1041320124. [DOI] [PubMed] [Google Scholar]
  4. Cutler R. G. Human longevity and aging: possible role of reactive oxygen species. Ann N Y Acad Sci. 1991;621:1–28. doi: 10.1111/j.1749-6632.1991.tb16965.x. [DOI] [PubMed] [Google Scholar]
  5. Fiorentini C., Arancia G., Paradisi S., Donelli G., Giuliano M., Piemonte F., Mastrantonio P. Effects of Clostridium difficile toxins A and B on cytoskeleton organization in HEp-2 cells: a comparative morphological study. Toxicon. 1989;27(11):1209–1218. doi: 10.1016/0041-0101(89)90029-9. [DOI] [PubMed] [Google Scholar]
  6. Fiorentini C., Chow S. C., Mastrantonio P., Jeddi-Tehrani M., Thelestam M. Clostridium difficile toxin A induces multinucleation in the human leukemic T cell line JURKAT. Eur J Cell Biol. 1992 Apr;57(2):292–297. [PubMed] [Google Scholar]
  7. Fiorentini C., Malorni W., Paradisi S., Giuliano M., Mastrantonio P., Donelli G. Interaction of Clostridium difficile toxin A with cultured cells: cytoskeletal changes and nuclear polarization. Infect Immun. 1990 Jul;58(7):2329–2336. doi: 10.1128/iai.58.7.2329-2336.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fiorentini C., Thelestam M. Clostridium difficile toxin A and its effects on cells. Toxicon. 1991;29(6):543–567. doi: 10.1016/0041-0101(91)90050-2. [DOI] [PubMed] [Google Scholar]
  9. Florin I., Thelestam M. Intoxication of cultured human lung fibroblasts with Clostridium difficile toxin. Infect Immun. 1981 Jul;33(1):67–74. doi: 10.1128/iai.33.1.67-74.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  11. Henriques B., Florin I., Thelestam M. Cellular internalisation of Clostridium difficile toxin A. Microb Pathog. 1987 Jun;2(6):455–463. doi: 10.1016/0882-4010(87)90052-0. [DOI] [PubMed] [Google Scholar]
  12. Hosey M. M., Lazdunski M. Calcium channels: molecular pharmacology, structure and regulation. J Membr Biol. 1988 Sep;104(2):81–105. doi: 10.1007/BF01870922. [DOI] [PubMed] [Google Scholar]
  13. Kurokowa M., Lynch K., Podolsky D. K. Effects of growth factors on an intestinal epithelial cell line: transforming growth factor beta inhibits proliferation and stimulates differentiation. Biochem Biophys Res Commun. 1987 Feb 13;142(3):775–782. doi: 10.1016/0006-291x(87)91481-1. [DOI] [PubMed] [Google Scholar]
  14. Larrick J. W., Wright S. C. Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J. 1990 Nov;4(14):3215–3223. doi: 10.1096/fasebj.4.14.2172061. [DOI] [PubMed] [Google Scholar]
  15. Lima A. A., Lyerly D. M., Wilkins T. D., Innes D. J., Guerrant R. L. Effects of Clostridium difficile toxins A and B in rabbit small and large intestine in vivo and on cultured cells in vitro. Infect Immun. 1988 Mar;56(3):582–588. doi: 10.1128/iai.56.3.582-588.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lyerly D. M., Krivan H. C., Wilkins T. D. Clostridium difficile: its disease and toxins. Clin Microbiol Rev. 1988 Jan;1(1):1–18. doi: 10.1128/cmr.1.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Malorni W., Fiorentini C., Paradisi S., Giuliano M., Mastrantonio P., Donelli G. Surface blebbing and cytoskeletal changes induced in vitro by toxin B from Clostridium difficile: an immunochemical and ultrastructural study. Exp Mol Pathol. 1990 Jun;52(3):340–356. doi: 10.1016/0014-4800(90)90074-n. [DOI] [PubMed] [Google Scholar]
  18. Nicotera P., Thor H., Orrenius S. Cytosolic-free Ca2+ and cell killing in hepatoma 1c1c7 cells exposed to chemical anoxia. FASEB J. 1989 Jan;3(1):59–64. doi: 10.1096/fasebj.3.1.2910738. [DOI] [PubMed] [Google Scholar]
  19. Orrenius S., Nicotera P. On the role of calcium in chemical toxicity. Arch Toxicol Suppl. 1987;11:11–19. doi: 10.1007/978-3-642-72558-6_2. [DOI] [PubMed] [Google Scholar]
  20. Pothoulakis C., Sullivan R., Melnick D. A., Triadafilopoulos G., Gadenne A. S., Meshulam T., LaMont J. T. Clostridium difficile toxin A stimulates intracellular calcium release and chemotactic response in human granulocytes. J Clin Invest. 1988 Jun;81(6):1741–1745. doi: 10.1172/JCI113514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Quaroni A., Wands J., Trelstad R. L., Isselbacher K. J. Epithelioid cell cultures from rat small intestine. Characterization by morphologic and immunologic criteria. J Cell Biol. 1979 Feb;80(2):248–265. doi: 10.1083/jcb.80.2.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Reed P. W., Lardy H. A. A23187: a divalent cation ionophore. J Biol Chem. 1972 Nov 10;247(21):6970–6977. [PubMed] [Google Scholar]
  23. Sullivan N. M., Pellett S., Wilkins T. D. Purification and characterization of toxins A and B of Clostridium difficile. Infect Immun. 1982 Mar;35(3):1032–1040. doi: 10.1128/iai.35.3.1032-1040.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Torres J., Jennische E., Lange S., Lönnroth I. Enterotoxins from Clostridium difficile; diarrhoeogenic potency and morphological effects in the rat intestine. Gut. 1990 Jul;31(7):781–785. doi: 10.1136/gut.31.7.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Trump B. F., Berezesky I. K. The role of cytosolic Ca2+ in cell injury, necrosis and apoptosis. Curr Opin Cell Biol. 1992 Apr;4(2):227–232. doi: 10.1016/0955-0674(92)90037-d. [DOI] [PubMed] [Google Scholar]

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

RESOURCES