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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
Author(s) -
Akaki Tatsuya,
Sato Katsumasa,
Shimizu Toshiaki,
Sano Chiaki,
Kajitani Hiroko,
Dekio Satoshi,
Tomioka Haruaki
Publication year - 1997
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.62.6.795
Subject(s) - biology , effector , biochemistry , arachidonic acid , stimulation , antagonism , receptor , endocrinology , enzyme
We studied microbicidal activities of reactive nitrogen intermediates (RNI), free fatty acids (FFA), and reactive oxygen intermediates (ROI) against Mycobacterium avium complex (MAC) and the mode of macrophage (mΦ) production of these effectors. (1) Intracellular growth of MAC in murine peritoneal mΦs was accelerated by scavengers for ROI or RNI and inhibitors of nitric oxide synthase or phospholipase A 2 , indicating roles of ROI, RNI, and FFA in mΦ anti‐MAC functions. (2) Acidified NaNO 2 ‐derived RNI, FFA (linolenic and arachidonic acids), and the H 2 O 2 ‐mediated halogenation system exhibited a significant anti‐MAC bactericidal activity. The combination of RNI with FFA showed a synergistic effect However, the H 2 O 2 ‐halogenation system in combination with either RNI or FFA showed an antagonism. When Listeria monocytogenes (Lm) was used as a target organism, the combinations of RNI + FFA and RNI + H 2 O 2 ‐halogenation gave a synergistic effect, whereas FFA + H 2 O 2 ‐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 potentiated. (3) ROI production by murine peritoneal mΦs was observed 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 36 h and continued at least for 4 days. These findings suggest that RNI and FFA rather than ROI are important effectors of anti‐MAC functions of mΦs, and the collaborating action of RNI with FFA temporarily participates in mΦ‐mediated killing of MAC in the relatively early phase after MAC stimulation. J. Leukoc. Biol . 62: 795–804; 1997.