EFFECTOR MOLECULES IN EXPRESSION OF THE ANTIMICROBIAL ACTIVITY OF MACROPHAGES AGAINST MYCOBACTERIUM-AVIUM COMPLEX - ROLES OF REACTIVE NITROGEN INTERMEDIATES, REACTIVE OXYGEN INTERMEDIATES, AND FREE FATTY-ACIDS

We studied microbicidal activities of reactive nitrogen intermediates (RNI), free fatty acids (FEA), and reactive oxygen intermediates (ROI) against Mycobacterium avium complex (MAC) and tile mode of macrophage (m phi) production of these effecters, (1) Intracellular growth of MA C in murine peritoneal m phi s was accelerated by scavengers for ROI o r RNI and inhibitors of nitric oxide synthase or phospholipase A(2), i ndicating roles of ROI, RNI, and FFA in m phi anti-MAC functions, (2) Acidified NaNO2-derived RNI, FFA (linolenic and arachidonic acids), an d the H2O2-mediated halogenation system exhibited a significant anti-M AC bactericidal activity, The combination of RNI with FFA showed a syn ergistic effect, However, the H2O2-halogenation system in combination with either RNI or FFA showed an antagonism, When Listeria monocytogen es (Lm) was used as a target organism, the combinations of RNI + FFA a nd RNI + H2O2-halogenation gave a synergistic effect, whereas FFA + H2 O2-halogenation showed an antagonism in exerting bactericidal activity , In addition, when ROI generated by the xanthine oxidase-acetaldehyde system was combined with RNI, anti-lm but not anti-MAC activity was p otentiated, (3) ROI production by murine peritoneal m phi s was observ ed immediately after contact with MAC organisms (MAC stimulation) and ceased within 2 h, FFA release was seen 1-24 h after MAC stimulation, RNI production was initiated from 3 h and increased during the first 3 6 h and continued at least for 4 days, These findings suggest that RNI and FFA rather than ROI are important effecters of anti-MAC functions of m phi s, and the collaborating action of RNI with FEA temporarily participates in m phi-mediated killing of MAC in the relatively early phase after MAC stimulation.