This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prina, E Articles by Kirschke, H Search for Related Content PubMed PubMed Citation Articles by Prina, E Articles by Kirschke, H

 Previous Article  |  Next Article 

Infect Immun. 1990 June; 58(6): 1730-1737

Localization and activity of various lysosomal proteases in Leishmania amazonensis-infected macrophages.

E Prina, J C Antoine, B Wiederanders and H Kirschke

Département de Physiopathologie Expérimentale, Unité d'Immunophysiologie Cellulaire de l'Institut Pasteur et du Centre National de la Recherche Scientifique, Paris, France.

ABSTRACT

In mammalian hosts, Leishmania amastigotes are obligatory intracellular parasites of macrophages and multiply within parasitophorous vacuoles of phagolysosomal origin. To understand how they escape the harmful strategies developed by macrophages to kill ingested microorganisms, it is important to obtain information on the functional state of parasitophorous vacuole. For this purpose, we studied the intracellular distribution and activity of host lysosomal proteases in rat bone marrow-derived macrophages infected with Leishmania amazonensis amastigotes. Localization of cathepsins B, H, L, and D was investigated by using specific immunoglobulins. In uninfected macrophages, these enzymes were located in perinuclear granules (most of them were probably secondary lysosomes) which, after infection, disappeared progressively. In infected macrophages, cathepsins were detected mainly in the parasitophorous vacuoles, suggesting that the missing secondary lysosomes had fused with these organelles. Biochemical assays of various proteases (cathepsins B, H, and D and dipeptidyl peptidases I and II) showed that infection was accompanied by a progressive increase of all activities tested, except that of dipeptidyl peptidase II, which remained constant. No more than 1 to 10% of these activities could be attributed to amastigotes. These data indicate that (i) Leishmania infection is followed by an increased synthesis and/or a reduced catabolism of host lysosomal proteases, and (ii) amastigotes grow in a compartment rich in apparently fully active proteases. Unexpectedly, it was found that infected and uninfected macrophages degraded endocytosed proteins similarly. The lack of correlation in infected macrophages between increase of protease activities and catabolism of exogenous proteins could be linked to the huge increase in volume of the lysosomal compartment.

---

Infect Immun. 1990 June; 58(6): 1730-1737

This article has been cited by other articles:

• Prina, E., Abdi, S. Z., Lebastard, M., Perret, E., Winter, N., Antoine, J.-C. (2004). Dendritic cells as host cells for the promastigote and amastigote stages of Leishmania amazonensis: the role of opsonins in parasite uptake and dendritic cell maturation. J. Cell Sci. 117: 315-325 [Abstract] [Full Text]  
• Nandan, D., Yi, T., Lopez, M., Lai, C., Reiner, N. E. (2002). Leishmania EF-1alpha Activates the Src Homology 2 Domain Containing Tyrosine Phosphatase SHP-1 Leading to Macrophage Deactivation. J. Biol. Chem. 277: 50190-50197 [Abstract] [Full Text]  
• Khan, N. A., Jarroll, E. L., Panjwani, N., Cao, Z., Paget, T. A. (2000). Proteases as Markers for Differentiation of Pathogenic and Nonpathogenic Species of Acanthamoeba. J. Clin. Microbiol. 38: 2858-2861 [Abstract] [Full Text]  
• Alexander, J, Satoskar, A., Russell, D. (1999). Leishmania species: models of intracellular parasitism. J. Cell Sci. 112: 2993-3002 [Abstract]  
• Schaible, U., Schlesinger, P., Steinberg, T., Mangel, W., Kobayashi, T, Russell, D. (1999). Parasitophorous vacuoles of Leishmania mexicana acquire macromolecules from the host cell cytosol via two independent routes. J. Cell Sci. 112: 681-693 [Abstract]  
• Cao, Z., Jefferson, D. M., Panjwani, N. (1998). Role of Carbohydrate-mediated Adherence in Cytopathogenic Mechanisms of Acanthamoeba. J. Biol. Chem. 273: 15838-15845 [Abstract] [Full Text]  
• Desjardins, M., Descoteaux, A. (1997). Inhibition of Phagolysosomal Biogenesis by the Leishmania Lipophosphoglycan. JEM 185: 2061-2068 [Abstract] [Full Text]  
• De Souza Leao, S, Lang, T, Prina, E, Hellio, R, Antoine, J. (1995). Intracellular Leishmania amazonensis amastigotes internalize and degrade MHC class II molecules of their host cells. J. Cell Sci. 108: 3219-3231 [Abstract]  
• Lang, T, Hellio, R, Kaye, P., Antoine, J. (1994). Leishmania donovani-infected macrophages: characterization of the parasitophorous vacuole and potential role of this organelle in antigen presentation. J. Cell Sci. 107: 2137-2150 [Abstract]  
• Lang, T, de Chastellier, C, Frehel, C, Hellio, R, Metezeau, P, Leao, S., Antoine, J. (1994). Distribution of MHC class I and of MHC class II molecules in macrophages infected with Leishmania amazonensis. J. Cell Sci. 107: 69-82 [Abstract]