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Bacterial toxin-induced pulmonary epithelial cytotoxicity and the protective effect of dibutyryl-cAMP


Bacterial infection is the most common cause of the adult respiratory distress syndrome which, in turn is associated with endothelial capillary permeability and alveolar oedema. Previously, we have demonstrated the direct cytotoxicity of the bacterial toxins Pseudomonas aeruginosa exotoxin A (Exo A) and Salmonella enteritidis lipopolysaccharide (LPS) on pulmonary endothelial cells. The purpose of this study was to investigate the effect of Exo A and LPS on pulmonary epithelial cells in vitro. We also tested the protective effect of dibutyryl cyclic adenosine monophosphate (db-cAMP) on Exo A-induced cytotoxicity. In cultured rat alveolar epithelial cells (RAEC) Exo A caused cytotoxicity as measured by51Cr release from these cells. LPS did not injure RAEC’s. Pretreatment of RAEC with db-cAMP (1mM) attenuated Exo A induced cytotoxicity. We conclude that (1) Exo A directly injures epithelial lung cells and may contribute to lung injury in cases of bacterial infection; (2) db-cAMP protects alveolar epithelial cells against Exo A-induced cytotoxicity and (3) alveolar epithelial cells in this model are resistant to LPS induced injury.

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  1. 1.

    Bernard, G. R., Artigas, A., Brigham, K. L., Carlet, J., Falke, K., Hudson, L., Lamy, M., Legall, J. R., Morris, A., Spragg, R. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes and clinical trials coordination. Am. J. Respir. Crit Care Med 1994; 149: 818–824

  2. 2.

    Sloane P. J., Gee M. H., Gottlieb J. E., Albertine K. H., Peters S. P., Burns R., Machiedo. G., Fish. J. E. A multicenter registry of patients with acute respiratory distress syndrome. Physiology and outcome. Am. Rev. Respir. Dis. 1992; 246: 419–426.

  3. 3.

    Brigham, K., Meyrick, B., Berry, L. C., Repine, J. E. Antioxidants protect cultured bovine lung endothelial cells from injury by endotoxin. J. Appl. Physiol. 1987; 63(2): 840–850.

  4. 4.

    Chang, S. W., Czartolomna, J., Voelkel, N. F. Role of eicosanoids in staphlyococcal alpha toxin-induced lung injury in the rat. Am. J. Physiol. 1992; 262: L502-L510.

  5. 5.

    Bourke, W. J., O’Connor, C. M., FitzGerald, M. X., McDonnell, T. J. Pseudomonas aeruginosa exotoxin A induces pulmonary endothelial cytotoxicity: protection by dibutyryl-cAMP. Eur. Respir. J. 1994; 7: 1754–1758.

  6. 6.

    Staub, N. C. Pulmonary edema due to increased microvascular permeability to fluid and protein. Circ. Res. 1978; 43: 43–51.

  7. 7.

    Adkins, W. K., Barnard, J. W., May, S., Seibert, A. F., Haynes, J., Taylor, A. E. Compounds that increase cAMP prevent ischemia-reperfusion pulmonary capillary injury. J. Appl. Physiol. 1992; 72: 492–497.

  8. 8.

    Simon, R. H., McCoy, J. P., Chu, A. E., Dehart, P. D., Goldstein, I. J. Binding of Griffonia simplicifolia I lectin to rat pulmonary alveolar macrophages and its use in purifying epithelial alveolar epithelial cells. Biochem. Biophys. Acta 1986; 885: 34–42.

  9. 9.

    Tobias, P. S., Soldan, K., Ulevitch, R. J. Isolation of lipopolysaccaride-binding acute phase reactant from rabbit serum. J. Exp. Med. 1986; 164: 777–783.

  10. 10.

    Dunn, M. M., Dunne, M.,Kamp, D.W. Polymorphonuclear leukocyte and Pseudomonas aeruginosa-induced damage to a human pulmonary epithelial cell line. J. Infec. Dis. 1990; 162: 172–177.

  11. 11.

    Iglewski, B. H., Kabat, D. NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin. Proc. Natl. Acad. Sci. USA 1975; 72: 2284–2288.

  12. 12.

    Hoffman, J., Hatherhill, J. R., Crowley, J., Harada, H., Yonemaru, M., Zhieng, H., Ishizaka, A., Raffin, T. A. Early post-treatment with pentoxifylline or dibutyryl-cAMP attenuates escherichia coli-induced acute lung injury in guinea pigs. Am. Rev. Respir. Dis. 1991; 143: 289–293.

  13. 13.

    Koyama, S., Toyofuku, T., Hirai, K., Yoshimura, K., Kobayashi, T. Dibutyryl cAMP attenuates lung responses induced by endotoxin in conscious sheep. Am. Rev. Respir. Dis. 1992; 146: 32–38.

  14. 14.

    Stelzner, T. J., Veil, J. V., O’Brien, R. F. Role of cyclic adenosine monophophosphate in the induction of endothelial barrier properties. J. Cell. Physiol. 1989; 139: 157–166.

  15. 15.

    Punjabi, C. J., Laskin, J. D., Pendino, K. J., Goller, N. L., Durham, S. K., Laskin, D. L. Production of nitric oxide by rat type II pneumocytes: increased expression of inducible nitric oxide synthase following inhalation of a pulmonary irritant. Am. J. Respir. Cell Mol. Biol. 1994; 11:165–172.

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Correspondence to W. Bourke or D. Kamp or M. Dunn or S-W. Chang.

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Bourke, W., Kamp, D., Dunn, M. et al. Bacterial toxin-induced pulmonary epithelial cytotoxicity and the protective effect of dibutyryl-cAMP. I.J.M.S. 167, 19–21 (1998).

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  • Acute Lung Injury
  • Alveolar Epithelial Cell
  • Adult Respiratory Distress Syndrome
  • Alveolar Oedema
  • Pulmonary Endothelial Cell