REPEATED INDUCTION OF NITRIC-OXIDE SYNTHASE AND LEISHMANICIDAL ACTIVITY IN MURINE MACROPHAGES

Murine macrophages express high levels of nitric oxide (NO) synthase a nd produce large amounts of NO when stimulated with interferon-gamma p lus lipopolysaccharide in vitro. The expression of NO synthase peaks a t 12 h after stimulation and declines rapidly to the background level by 72 h. These macrophages can be repeatedly reactivated to express si milar levels of NO synthase. The reactivation is not due to newly divi ded cells since peritoneal macrophages which do not divide in vitro an d J774 cells cultured in the presence of colchicine can also be restim ulated to express NO synthase. The reactivation is accompanied by re-e xpression of NO synthase mRNA, as assessed by polymerase chain reactio n analysis. Furthermore, the reactivated macrophages are fully capable of killing the intracellular protozoan parasite Leishmania major.