Intracellular parasite killing induced by electron carriers. I. Effect of electron carriers on intracellular Leishmania spp. in macrophages from different genetic backgrounds.

Mouse peritoneal macrophages were infected with Leishmania parasites from different species, then exposed to the electron carriers methylene blue (MB), toluidine blue O (TB), phenazine methosulfate (PMS) and crystal violet (CV). This led to killing of the intracellular parasites with no harm to the macrophages. On a molar basis, the potency of the electron carriers decreased in the following order: CV, TB, MB and PMS. MB and TB were more active against intracellular compared to free parasites, suggesting that the macrophages themselves might play a role in the observed anti-parasite toxicity. Intracellular killing could be achieved by a short pulse (30 min) of electron carrier. No difference could be detected between macrophages from different mouse strains as regards their capacity to kill intracellular parasites upon incubation with electron carriers. When macrophages from the L. major susceptible ('non-healer') BALB/c strain were infected with either L. enriettii (which is nonpathogenic to mice) or L. major, then exposed to an activating, lymphokine-rich supernatant, destruction of only L. enriettii was achieved, whereas L. major survived intracellularly. Incubation with MB, however, led to intracellular destruction of both parasites. Other Leishmania species could also be killed irrespective of the genetic background of the macrophages. These observations suggest that the triggering events in electron carrier- and lymphokine-mediated intracellular parasite killing are different.