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.
Ponte-Sucre
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Laboratory of Molecular Physiology, Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas. aiponte@reacciun.ve
Figarella
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Moll
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D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D005905:Glyburide / Q000627:therapeutic use*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D018320:Leishmania major / Q000187:drug effects / Q000254:growth & development; D007896:Leishmaniasis / Q000188:drug therapy* / Q000276:immunology* / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology* / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C
D015703:Antigens, CD; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D005905:Glyburide