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Parasitology Research

, Volume 87, Issue 1, pp 27–31 | Cite as

Experimental leishmaniasis: synergistic effect of ion channel blockers and interferon-γ on the clearance of Leishmania major by macrophages

  • Alicia Ponte-Sucre
  • Alexis Mendoza-León
  • Heidrun Moll
ORIGINAL PAPER

Abstract

We have previously shown that cultured Leishmania promastigotes are sensitive to drugs blocking K+ and Na+ channels and Na+/H+ transport systems and that the percentage of parasite-infected macrophages decreases significantly in the presence of the drugs. In the present work, we analyzed whether this drug susceptibility of intracellular amastigotes was associated with the activation of macrophage microbicidal mechanisms. Pretreatment of the cells with glibenclamide (GLIB) increased their resistance to infection with Leishmania, an effect that may be mediated by calcium fluxes since it was reversed by ethylene glycol bis-(β-aminoethyl ether)-N,N,N′,N-tetraacetic acid (EGTA). It was noteworthy that in infected macrophages posttreated with the drugs the clearance of parasites was strongly enhanced when the cells were treated simultaneously with GLIB and interferon-γ; this effect correlated with an increased production of reactive nitrogen intermediates. In conclusion, the data suggest that GLIB treatment increases the resistance of macrophages to infection with Leishmania and potentiates the interferon-γ-stimulated clearance of parasites via the induction of nitric oxide.

Keywords

Nitric Oxide Ethylene Glycol Transport System Channel Blocker EGTA 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2001

Authors and Affiliations

  • Alicia Ponte-Sucre
    • 1
  • Alexis Mendoza-León
    • 3
  • Heidrun Moll
    • 2
  1. 1.Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Apdo 68256, Caracas 1062-A, Venezuela e-mail: alponte@reaccium.de Tel.: +58-2-6053665; Fax: 58-2-6934351VE
  2. 2.Institute for Molecular Biology of Infectious Diseases, University of Wuerzburg, Roentgenring 11, 97070 Wuerzburg, GermanyDE
  3. 3.Laboratory of Biochemical and Molecular Biology of Parasites, Instituto de Biología Experimental, Facultad de Ciencias, Universidad Central de Venezuela, Apdo 47577, Caracas 1041-A, VenezuelaVE

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