SummaryLeishmania major promastigotes were found to avoid activation of mouse bone marrow-derived macrophages (BMMo) in vitro for production of cytokines that are typically induced during infection with other intracellular pathogens. Coexposure of BMMo to the parasite and other microbial stimuli resulted in complete inhibition ofinterleukin (IL) 12 (p40) mRNA induction and IL-12 release. In contrast, mRNA and protein levels for IL-lot, IL-113, tumor necrosis factor (TNF) ci, and inducible NO synthase (iNOS) were only partially reduced, and signals for IL-10 and monocyte chemoattractant protein (MCP-1/JE) were enhanced. The parasite could provide a detectable trigger for TNF-cx and iNOS in BMMo primed with interferon (IFN) y,
Two isolates (skin and lymph node) of Leishmania infantum obtained from a naturally infected dog were cloned and the free pools of polyamines for both complete isolates and clones were determined. Putrescine (Put) and spermidine (Spd) levels were highly variable among the lines studied, ranging from 0.89 to 2.1 nmol Spd/10(7) promastigotes. The Put/Spd ratio was also variable (1.54-0.51) and correlated with the cell growth of the lines studied. There were important differences in the clones' sensitivities to difluoromethylornithine (DFMO) and Berenil, with some of the clones being almost refractory to the inhibitory effect of 50 microM DFMO, whereas the growth of others was reduced by 60%; similar findings were obtained with 50 microM Berenil. L. infantum sensitivities to DFMO and Berenil were correlated and apparently related to the values for the Put/Spd index.
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