Lipoarabinomannan from Mycobacterium tuberculosis modulates the generation of reactive nitrogen intermediates by gamma interferon-activated macrophages

Abstract

Lipoarabinomannan derived from the virulent Erdman strain and a rapidly growing, laboratory-attenuated strain of Mycobacterium tuberculosis were evaluated for their ability to modulate the production of nitric oxide (NO) by macrophages activated with IFN-γ or IFN-γ and LPS. It was observed that in macrophages pretreated with 100 µg ml−1 LAM, the NO induced by IFN-γ alone was augmented while the NO induced by IFN-γ and LPS was reduced. LAM was also shown to synergize with IFN-γ in the induction of NO, with AraLAM from the attenuated strain exhibiting greater potency than ManLAM from the Erdman strain. Despite the modulation of NO production, LAM did not affect the IFN-γ-induced macrophage growth inhibition of Francisella tularensis LVS, an organism whose growth inhibition in activated macrophages is dependent upon NO.