Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1996 Jan;64(1):358–362. doi: 10.1128/iai.64.1.358-362.1996

Phospholipase C and perfringolysin O from Clostridium perfringens upregulate endothelial cell-leukocyte adherence molecule 1 and intercellular leukocyte adherence molecule 1 expression and induce interleukin-8 synthesis in cultured human umbilical vein endothelial cells.

A E Bryant 1, D L Stevens 1
PMCID: PMC173769  PMID: 8557365

Abstract

Clostridium perfringens phospholipase C (PLC) and perfringolysin O (PFO) differentially induced human umbilical vein endothelial cell expression and synthesis of endothelial cell-leukocyte adherence molecule-1 (ELAM-1), intracellular leukocyte adherence molecule-1 (ICAM-1), and interleukin-8 (IL-8). PLC strongly induced expression of ELAM-1, ICAM-1, and IL-8, while PFO stimulated early ICAM-1 expression but did not promote ELAM-1 expression or IL-8 synthesis. PLC caused human umbilical vein endothelial cells to assume a fibroblastoid morphology, whereas PFO, in high concentrations or after prolonged low-dose toxin exposure, caused cell death. The toxin-induced expression of proadhesive and activational proteins and direct cytopathic effects may contribute to the leukostasis, vascular compromise, and capillary leak characteristics of C. perfringens gas gangrene.

Full Text

The Full Text of this article is available as a PDF (249.3 KB).

Selected References

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

  1. Asmuth D. M., Olson R. D., Hackett S. P., Bryant A. E., Tweten R. K., Tso J. Y., Zollman T., Stevens D. L. Effects of Clostridium perfringens recombinant and crude phospholipase C and theta-toxin on rabbit hemodynamic parameters. J Infect Dis. 1995 Nov;172(5):1317–1323. doi: 10.1093/infdis/172.5.1317. [DOI] [PubMed] [Google Scholar]
  2. Bevilacqua M. P. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol. 1993;11:767–804. doi: 10.1146/annurev.iy.11.040193.004003. [DOI] [PubMed] [Google Scholar]
  3. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bogen S., Pak J., Garifallou M., Deng X., Muller W. A. Monoclonal antibody to murine PECAM-1 (CD31) blocks acute inflammation in vivo. J Exp Med. 1994 Mar 1;179(3):1059–1064. doi: 10.1084/jem.179.3.1059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bryant A. E., Bergstrom R., Zimmerman G. A., Salyer J. L., Hill H. R., Tweten R. K., Sato H., Stevens D. L. Clostridium perfringens invasiveness is enhanced by effects of theta toxin upon PMNL structure and function: the roles of leukocytotoxicity and expression of CD11/CD18 adherence glycoprotein. FEMS Immunol Med Microbiol. 1993 Dec;7(4):321–336. doi: 10.1111/j.1574-695X.1993.tb00414.x. [DOI] [PubMed] [Google Scholar]
  6. Colden-Stanfield M., Ratcliffe D., Cramer E. B., Gallin E. K. Characterization of influenza virus-induced leukocyte adherence to human umbilical vein endothelial cell monolayers. J Immunol. 1993 Jul 1;151(1):310–321. [PubMed] [Google Scholar]
  7. McEver R. P., Beckstead J. H., Moore K. L., Marshall-Carlson L., Bainton D. F. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest. 1989 Jul;84(1):92–99. doi: 10.1172/JCI114175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Muller W. A., Weigl S. A., Deng X., Phillips D. M. PECAM-1 is required for transendothelial migration of leukocytes. J Exp Med. 1993 Aug 1;178(2):449–460. doi: 10.1084/jem.178.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Patel K. D., Lorant E., Jones D. A., Prescott M., McIntyre T. M., Zimmerman G. A. Juxtacrine interactions of endothelial cells with leukocytes: tethering and signaling molecules. Behring Inst Mitt. 1993 Aug;(92):144–164. [PubMed] [Google Scholar]
  10. Pober J. S., Gimbrone M. A., Jr, Lapierre L. A., Mendrick D. L., Fiers W., Rothlein R., Springer T. A. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed] [Google Scholar]
  11. Stevens D. L., Mitten J., Henry C. Effects of alpha and theta toxins from Clostridium perfringens on human polymorphonuclear leukocytes. J Infect Dis. 1987 Aug;156(2):324–333. doi: 10.1093/infdis/156.2.324. [DOI] [PubMed] [Google Scholar]
  12. Stevens D. L., Troyer B. E., Merrick D. T., Mitten J. E., Olson R. D. Lethal effects and cardiovascular effects of purified alpha- and theta-toxins from Clostridium perfringens. J Infect Dis. 1988 Feb;157(2):272–279. doi: 10.1093/infdis/157.2.272. [DOI] [PubMed] [Google Scholar]
  13. Sticherling M., Hetzel F., Schröder J. M., Christophers E. Time- and stimulus-dependent secretion of NAP-1/IL-8 by human fibroblasts and endothelial cells. J Invest Dermatol. 1993 Oct;101(4):573–576. doi: 10.1111/1523-1747.ep12366023. [DOI] [PubMed] [Google Scholar]
  14. Stolpen A. H., Guinan E. C., Fiers W., Pober J. S. Recombinant tumor necrosis factor and immune interferon act singly and in combination to reorganize human vascular endothelial cell monolayers. Am J Pathol. 1986 Apr;123(1):16–24. [PMC free article] [PubMed] [Google Scholar]
  15. Tso J. Y., Siebel C. Cloning and expression of the phospholipase C gene from Clostridium perfringens and Clostridium bifermentans. Infect Immun. 1989 Feb;57(2):468–476. doi: 10.1128/iai.57.2.468-476.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tweten R. K. Cloning and expression in Escherichia coli of the perfringolysin O (theta-toxin) gene from Clostridium perfringens and characterization of the gene product. Infect Immun. 1988 Dec;56(12):3228–3234. doi: 10.1128/iai.56.12.3228-3234.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tweten R. K. Nucleotide sequence of the gene for perfringolysin O (theta-toxin) from Clostridium perfringens: significant homology with the genes for streptolysin O and pneumolysin. Infect Immun. 1988 Dec;56(12):3235–3240. doi: 10.1128/iai.56.12.3235-3240.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Whatley R. E., Nelson P., Zimmerman G. A., Stevens D. L., Parker C. J., McIntyre T. M., Prescott S. M. The regulation of platelet-activating factor production in endothelial cells. The role of calcium and protein kinase C. J Biol Chem. 1989 Apr 15;264(11):6325–6333. [PubMed] [Google Scholar]
  19. Zimmerman G. A., McIntyre T. M., Prescott S. M., Otsuka K. Brief review: molecular mechanisms of neutrophil binding to endothelium involving platelet-activating factor and cytokines. J Lipid Mediat. 1990;2 (Suppl):S31–S43. [PubMed] [Google Scholar]

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

RESOURCES