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Destruction of intracellular and isolated Leishmania mexicana amazonensis amastigotes by amino acid amides

Published online by Cambridge University Press:  06 April 2009

M. Rabinovitch  and
V. Zilberfarb
M. Rabinovitch
Affiliation:
Unité d'Immunophysiologie Cellulaire, Institut Pasteur, and Centre National de la Recherche Scientifique (UA 04 1113), 25 Rue du Docteur Roux, 75724 Paris, France
V. Zilberfarb
Affiliation:
Unité d'Immunophysiologie Cellulaire, Institut Pasteur, and Centre National de la Recherche Scientifique (UA 04 1113), 25 Rue du Docteur Roux, 75724 Paris, France
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Summary

L-amino acid esters such as leucine methyl ester (Leu-OMe) destroy Leishmania mexicana amazonensis amastigotes by a mechanism which may involve hydrolysis of the compounds by parasite enzymes. Moreover, several esters (e.g. Ile-OMe) prevent the killing of parasites by Leu-OMe, perhaps by inhibition of the hydrolytic enzymes. We show here that certain amino acid amides are also leishmanicidal. Killing of Leishmania within macrophages was assessed microscopically, and that of isolated amastigotes was measured by reduction of the tetrazolium MTT. Amino acid amides were generally less active than the methyl esters and several were more toxic to the macrophages, as determined by inspection of Giemsa-stained preparations. Ranks of activity of the amides on isolated amastigotes were Trp > Leu > Phe > Met > Tyr. The amides of Ala, Gly, Val, Ile, His and D-Leu were inactive. This pattern of activity is similar to that of amino acid methyl esters. Ile-NH2 and a few other amides protected intracellular as well as isolated parasites from killing by Leu-OMe. Conversely, Ile-OMe reduced the toxicity of Leu-NH2 for isolated amastigotes. None of the esters or amides assayed prevented the destruction of Leishmania by Trp-NH2. The results are compatible with the view that amino acid esters and amides may be recognized by the same or similar parasite enzymes.

Type
Research Article
Information
Parasitology , Volume 96 , Issue 2 , April 1988 , pp. 289 - 296
Copyright
Copyright © Cambridge University Press 1988

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References

REFERENCES

Alfieri, S., Zilberfarb, V. & Rabinovitch, M. (1987). Destruction of Leishmania mexicana amazonensis by leucine methyl ester: protection by other amino acid esters. Parasitology 95, 31–41.CrossRefGoogle ScholarPubMed
Carmichael, J., DeGraff, W. G., Gazdar, A. F., Minna, J. D. & Mitchell, J. B. (1987). Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Research 47, 936–42.Google ScholarPubMed
Denizot, F. & Lang, R. (1986). Rapid colorimetric assay for cell growth and survival. Modifications of the tetrazolium dye procedure giving improved sensitivity and reliability. Journal of Immunological Methods 89, 271–7.CrossRefGoogle ScholarPubMed
Goldman, R. & Kaplan, A. (1973). Rupture of rat liver lysosomes mediated by L-amino acid esters. Biochimica et Biophysica Acta 318, 205–316.CrossRefGoogle ScholarPubMed
Knight, C. G. (1977). Principles of the design and use of synthetic substrates and inhibitors of tissue proteinases. In Proteinases in Mammalian Cells and Tissues (ed. Barrett, A. J.), pp. 583–636. Amsterdam: North-Holland.Google Scholar
Mosmann, T. (1983). Rapid colorimetric assay for cellular growth and survival: application for proliferation and cytotoxicity assays. Journal of Immunological Methods 65, 55–63.CrossRefGoogle ScholarPubMed
Neal, R. A. & Croft, S. L. (1984). An in-vitro system for determining the activity of compounds against the intracellular amastigote form of Leishmania donovani. Journal of Antimicrobial Therapy 14, 463–75.CrossRefGoogle ScholarPubMed
Rabinovitch, M., Zilberfarb, V. & Pouchelet, M. (1987). Leishmania mexicana: killing of isolated amastigotes by amino acid esters. American Journal of Tropical Medicine and Hygiene 36, 288–95.CrossRefGoogle ScholarPubMed
Rabinovitch, M., Zilberfarb, V. & Ramazeilles, C. (1986). Destruction of Leishmania mexicana amazonensis amastigotes within macrophages by lysosomotropic amino acid esters. Journal of Experimental Medicine 163, 520–35.CrossRefGoogle ScholarPubMed
Ransom, J. T. & Reeves, J. P. (1983). Accumulation of amino acids within intracellular lysosomes of rat polymorphonuclear leukocytes incubated with amino acid methyl esters. Journal of Biological Chemistry 258, 9270–5.CrossRefGoogle ScholarPubMed
Reeves, J. P. (1979). Accumulation of amino acids by lysosomes incubated with amino acid methyl esters. Journal of Biological Chemistry 254, 8914–21.CrossRefGoogle ScholarPubMed
Thiele, D. L., Kurosaka, M. & Lipsky, P. E. (1983). Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. Journal of Immunology 131, 2282–90.CrossRefGoogle Scholar
Thiele, D. L. & Lipsky, P. (1986). The immunosuppressive activity of L-leucyl-L-leucine methyl ester: selective ablation of cytotoxic lymphocytes and monocytes. Journal of Immunology 136, 1038–48.CrossRefGoogle ScholarPubMed