Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-10T11:58:49.536Z Has data issue: false hasContentIssue false
  • English
  • Français

Cytotoxic activity of 13-hydroxyoctadecadienoic acid against Toxoplasma gondii

Published online by Cambridge University Press:  06 April 2009

W. R. Henderson Jr  and
E. Y. Chi
W. R. Henderson Jr
Affiliation:
Departments of Medicine, University of Washington, Seattle, WA 98195, USA
E. Y. Chi
Affiliation:
Departments of Pathology, University of Washington, Seattle, WA 98195, USA
Get access Rights & Permissions [Opens in a new window]

Summary

Recent data indicate that platelets may play an important role in the host defence against Toxoplasma gondii infections. T. gondii-stimulated human platelets release thromboxane A2 (TXA2) and 12-hydroxyeicosatetraenoic acid (12-HETE) from arachidonic acid and 13-hydroxyoctadecadienoic acid (13-HODE) from linoleic acid (Yong et al. 1991; Henderson et al. 1992). We have previously demonstrated that the eicosanoid TXA2 has potent cytotoxic activity against T. gondii trophozoites (Yong et al. 1991). In this study, we examined whether 12-HETE, 13-HODE, and linoleic acid also have toxoplasmacidal activity. 13-HODE at concentrations ≥ 10−8 M rapidly induced cytotoxic changes in T. gondii. Ultrastructural changes induced by 13-HODE in T. gondii included an initial leakage of cytoplasmic contents into a space between the inner and outer parasite bilayer membrane units which was followed by intracellular vacuolation and loss of cytoplasmic contents. In contrast, linoleic acid and 12-HETE lacked toxoplasmacidal activity at 10−10–10−6 M concentrations. These data indicate that 13-HODE, a product of linoleic acid metabolism, has potent cytotoxic activity against T. gondii; this toxoplasmacidal activity may be important in the inflammatory response to this pathogen.

Keywords

Toxoplasma gondii, cytotoxicity, 13-hydroxyoctadecadienoic acid (13-HODE), linoleic acid, 12-hydroxyeicosatetraenoic acid (12-HETE), thromboxane A2 (TXA2)
Type
Research Article
Information
Parasitology , Volume 105 , Issue 3 , December 1992 , pp. 343 - 347
Copyright
Copyright © Cambridge University Press 1992

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Beverley, J. K. A. (1959). Congenital transmission of toxoplasmosis through successive generations of mice. Nature, London 183, 1348–9.CrossRefGoogle ScholarPubMed
Buchanan, M. R., Haas, T. A., Lagarde, M. & Guichardant, M. (1985). 13-Hydroxyoctadecadienoic acid is the vessel wall chemorepellant factor, LOX. Journal of Biological Chemistry 260, 16056–9.CrossRefGoogle ScholarPubMed
Engels, F., Willems, H. & Nijkamp, F. P. (1986). Cyclooxygenase-catalyzed formation of 9-hydroxylinoleic acid by guinea-pig alveolar macrophages under non-stimulated conditions. FEBS Letters 209, 249–53.CrossRefGoogle ScholarPubMed
Hatcher, F. M. & Kuhn, R. E. (1982). Destruction of Trypanosoma cruzi by natural killer cells. Science 218, 295–6.CrossRefGoogle ScholarPubMed
Henderson, W. R., Chi, E. Y. & Klebanoff, S. J. (1980). Eosinophil peroxidase-induced mast cell secretion. Journal of Experimental Medicine 152, 265–79.CrossRefGoogle ScholarPubMed
Henderson, W. R. Jr., Rashed, M., Yong, E. C., Fritsche, T. R. & Chiang, G. K. (1992). Toxoplasma gondii stimulates the release of 13- and 9-hydroxyoctadecadienoic acids by human platelets. Biochemistry 31, 5356–62.CrossRefGoogle ScholarPubMed
Kaduce, T. L., Figard, P. H., Leifur, R. & Spector, A. A. (1989). Formation of 9-hydroxyoctadecadienoic acid from linoleic acid in endothelial cells. Journal of Biological Chemistry 264, 6823–30.CrossRefGoogle Scholar
Locksley, R. M., Fankhauser, J. & Henderson, W. R. (1985). Alteration of leukotriene release by macrophages ingesting Toxoplasma gondii. Proceedings of the National Academy of Sciences, USA 82, 6922–6.CrossRefGoogle ScholarPubMed
Murray, H. W., Rubin, B. Y., Carriero, S. M., Harris, A. M. & Jaffee, E. A. (1985). Human mononuclear phagocyte antiprotozoal mechanisms oxygen-dependent vs oxygen-independent activity against intracellular Toxoplasma gondii. Journal of Immunology 134, 1982–8.CrossRefGoogle ScholarPubMed
Raizman, R. E. & Neva, F. A. (1975). Detection of circulating antigen in acute experimental infections with Toxoplasma gondii. Journal of Infectious Diseases 132, 44–8.CrossRefGoogle ScholarPubMed
Remington, J. S. (1961). Experiments on the transmission of toxoplasmosis. Survey of Ophthalamology 6, 856–67.Google ScholarPubMed
Remington, J. S. & Desmonts, G. (1990). Toxoplasmosis. In Infectious Diseases of the Fetus and Newborn Infant (ed. Remington, J. S. & Klein, J. O), pp. 89–195. Philadelphia: W. B. Saunders.Google Scholar
Ridel, P.-R., Auriault, C., Darcy, F., Pierce, R. J., Leite, P., Santoro, F., Neyrinck, J.-L., Kusnierz, J.-P. & Capron, A. (1988). Protective role of the IgE in immunocompromised rat toxoplasmosis. Journal of Immunology 141, 978–83.CrossRefGoogle ScholarPubMed
Siegel, S. E., Lunde, M. N., Gelderman, A. H., Halterman, R. H., Brown, J. A., Levine, A. S. & Graw, R. G. JR. (1971). Transmission of toxoplasmosis by leukocyte transfusion. Blood 37, 388–94.CrossRefGoogle ScholarPubMed
Soberman, R. J., Harper, T. W., Betteridge, D., Lewis, R. A. & Austen, K. F. (1985). Characterization and separation of the arachidonic acid 5-lipoxygenase and linoleic acid ω-6 lipoxygenase (arachidonic acid 15-lipoxygenase) of human polymorphonuclear leukocytes. Journal of Biological Chemistry 260, 4508–15.CrossRefGoogle ScholarPubMed
Suzuki, Y., Orellana, M. A., Schreiber, R. D. & Remington, J. S. (1988). Interferon-γ: the major mediator of resistance against Toxoplasma gondii. Science 240, 516–18.CrossRefGoogle ScholarPubMed
Verlinde, J. D. & Makstenieks, O. (1950). Repeated isolation of Toxoplasma from the cerebrospinal fluid and from the blood, and the antibody response in four cases of congenital toxoplasmosis. Antonie van Leeuwenhoek (Wageningen) 16, 366–72.CrossRefGoogle ScholarPubMed
Weibel, E. R. (1979). Stereological methods. In Practical Methods for Biologic Morphometry, vol. 1, pp. 162–203. London: Academic Press.Google Scholar
Wilson, C. B. & Remington, J. S. (1979). Activity of human blood leukocytes against Toxoplasma gondii. Journal of Infectious Diseases 140, 890–5.CrossRefGoogle ScholarPubMed
YamajaSetty, B. N. Setty, B. N., Berger, M. & Stuart, M. J. (1987). 13-Hydroxyoctadecadienoic acid (13-HODE) stimulates prostacyclin production by endothelial cells. Biochemical and Biophysical Research Communications 146, 502–9.Google Scholar
Yong, E. C., Chi, E. Y., Fritsche, T. R. & Henderson, W. R. JR (1991). Human platelet-mediated cytotoxicity against Toxoplasma gondii: role of thromboxane. Journal of Experimental Medicine 173, 65–78.CrossRefGoogle ScholarPubMed