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Relations between resistance to chloroquine and acidification of endocytic vesicle of Plasmodium berghei

Published online by Cambridge University Press:  06 April 2009

J. Mahmalgi
Affiliation:
INSERM U.42, Biologie et Biochimie Parasitaire et Fongique, Villeneuve d'Ascq, FR
E. Veignie
Affiliation:
INSERM U.42, Biologie et Biochimie Parasitaire et Fongique, Villeneuve d'Ascq, FR
G. Prensier
Affiliation:
INSERM U.42, Biologie et Biochimie Parasitaire et Fongique, Villeneuve d'Ascq, FR
S. Moreau*
Affiliation:
INSERM U.42, Biologie et Biochimie Parasitaire et Fongique, Villeneuve d'Ascq, FR
*
*Reprint requests to Dr S. Moreau.

Summary

In order to visualize low-pH compartments of Plasmodium berghei strains we have used a basic congener of dinitrophenol, 3-(2,4-dinitroanilino)-3'-amino-N-methyldipropylamine (DAMP) which concentrates in acidic compartments, and can be detected by immunocytochemistry with anti-dinitrophenol antibodies. We have demonstrated that in a P. berghei chloroquine-sensitive strain (N strain), DAMP accumulates in the endocytic vacuoles where haemoglobin degradation is occurring. These compartments which have recently been shown to concentrate 4-aminoquinoline drugs (Moreau, Prensier, Maalla & Fortier, 1986) have an acidic pH. Conversely DAMP was found scattered all over the cytoplasm in a P. berghei chloroquine-resistant strain; the same phenomenon was previously observed (Moreau et al. 1986) in the localization of a 4-aminoquinoline on this same strain. Monensin-induced swelling of acidic compartments (Boss & Morre, 1984) was used as a complementary method for the determination of low-pH compartments on P. berghei strains. All the data reported here suggest that chloroquine resistance in P. berghei RC may be related to an impairment in the acidification of endocytic vesicles.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1989

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