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PubMed2001

Experimental leishmaniasis: the glibenclamide-triggered decrease in parasite growth correlates with changes in macrophage features.

Previous studies from our laboratories revealed the susceptibility of Leishmania sp. to glibenclamide (GLIB), a potassium channel blocker which selectively interacts with adenosine-binding-cassette transporters. In the present work, we analyzed whether the drug sensitivity of intracellular amastigotes correlates with changes in macrophage features that are related to their function as antigen-presenting cells. We provide evidence that in BALB/c murine macrophages, GLIB induced a decrease in the interferon-gamma-stimulated expression of major histocompatibility complex class II molecules and the co-stimulatory molecule CD86 (B7-2). Furthermore, it caused a decrease in the interleukin-1 secretion by macrophages. The data indicate that the treatment with GLIB inhibits the Th2 development and polarizes macrophage functions towards the induction of a protective Th1 response.

Animals↗

PubMed2000

Changes in the infectivity, pyruvate kinase activity, acid phosphatase activity and P-glycoprotein expression in glibenclamide-resistant Leishmania mexicana.

We previously demonstrated susceptibility of Leishmania sp. to glibenclamide, a K+ -ATP transport blocker which interacts with members of the superfamily of adenosine 5' triphosphate-binding cassette transporters. In order to characterize the molecular differences between a sensitive Leishmania strain, NR(Gs), and an experimentally selected glibenclamide-resistant strain, NR(Gr), specific biochemical and functional parameters have been evaluated both in the wild type and in the resistant strain. Most noteworthy, NR(Gr) exhibit an increased expression of P-glycoprotein and a decreased activity of functional key enzymes such as acid phosphatase, a prominent virulent factor of the parasite, and pyruvate kinase, a key control enzyme for both carbohydrate and protein metabolism. The specific biochemical, metabolic and functional changes observed in the resistant strain correlated with a reduced infectivity of stationary phase NR(Gr) in J774 macrophages and suggested a mechanism to overcome the effect of glibenclamide.

ATP Binding Cassette Transporter, Subfamily B, Mem↗