EFFECTOR MOLECULES OF THE HOST-DEFENSE MECHANISM AGAINST MYCOBACTERIUM-AVIUM COMPLEX - THE EVIDENCE SHOWING THAT REACTIVE OXYGEN INTERMEDIATES, REACTIVE NITROGEN INTERMEDIATES, AND FREE FATTY-ACIDS EACH ALONE ARE NOT DECISIVE IN EXPRESSION OF MACROPHAGE ANTIMICROBIAL ACTIVITY AGAINST THE PARASITES

In this study, we evaluated the roles of reactive oxygen intermediates (ROI), reactive nitrogen intermediates (RNI), and free fatty acids (F FA) as effecters of the macrophage-mediated host defence mechanism aga inst Mycobacterium avium complex (MAC). First, M. avium (three strains ) and M. intracellulare (two strains) were treated with the H2O2-Fe2+- mediated halogenation system, acidified NaNO2-derived RNI, or FFA (lin olenic acid) in sodium acetate buffer pH 5.5, and then counted for the number of residual colony-forming units (CFU) of organisms. Although these effecters exerted strong bactericidal activity against the MAC, the susceptibility of test organisms markedly varied from strain to st rain. There was no significant relationship between the degree of resi stance of a given MAC strain to these effecters and its virulence in m ice, indicating that ROI, RNI, and FFA each alone are not decisive as the effector components of the host defence mechanism against the MAC. Second, the increase in ROI-producing ability in murine peritoneal ma crophages due to tumour necrosis factor-alpha (TNF-alpha) treatment wa s not accompanied by parallel potentiation of anti-MAC activity of the same macrophage population. This excludes the possibility that ROI pl ay a central role in macrophage-mediated killing and inhibition of MAC organisms. Third, anti-MAC activity of BAM3 macrophage cell line was not significantly attenuated by N-G-monomethyl-L-arginine (NO synthase -inhibitor causing reduction of RNI production) or by quinacrine (phos pholipase A(2)-inhibitor causing reduction of FFA release), indicating that RNI and FFA each alone do not play crucial roles in the expressi on of macrophage antimicrobial activity against the MAC. The present f indings suggest important roles of collaborating actions of various an timicrobial effecters and/or the participation of other kinds of effec ters in macrophage-mediated killing and inhibition of MAC organisms.