MURINE EPIDERMAL LANGERHANS-CELLS DO NOT EXPRESS INDUCIBLE NITRIC-OXIDE SYNTHASE

In Leishmania-infected macrophages (M Phi), the formation of reactive nitrogen intermediates by the inducible isoform of nitric oxide syntha se (iNOS) is critical for the killing of the intracellular parasites. We have recently shown that, in addition to M Phi, epidermal Langerhan s cells (LC) can phagocytose Leishmania major, but they do not allow p arasite replication. Therefore, we analyzed whether LC and M Phi displ ay the same leishmanicidal effector mechanism. Unlike M Phi, stimulati on of unselected epidermal cells with interferon-gamma/lipopolysacchar ide did not lead to the release of nitric oxide (NO), and inhibition o f NO production had no effect on the rate of infection of LC. iNOS mRN A was clearly detectable in M Phi as well as unselected epidermal cell s (the majority of which consists of keratinocytes) after stimulation with different cytokines. In contrast, pure LC obtained by single-cell picking from cytokine-activated or L. major- infected epidermal cells did not express iNOS mRNA. Addition of the WO donor S-nitroso-N-acety lpenicillamine to already-infected LC did not alter their rate of infe ction, indicating that LC do not utilize exogenous NO for the control of intracellular Leishmania. These results suggest that in the L. majo r-infected skin. activated M Phi and keratinocytes, bur nor LC have th e ability to express iNOS activity. Therefore, an as yet unidentified. NO-independent mechanism appears to be responsible for the control of parasite replication in LC.