Effects of picolinic acid on the antimicrobial functions of host macrophages against Mycobacterium avium complex.
Picolinic acid (PA) potentiates macrophage (MPhi) antimicrobial activity against intracellular Mycobacterium avium complex (MAC). Here, we studied the mechanisms of this phenomenon using human THP-1 MPhis. First, when PA-treated MAC-infected MPhis were cultured in the presence or absence of reactive oxygen intermediate (ROI) scavengers, nitric oxide synthase (NOS) inhibitors or phospholipase A(2) (PLA(2)) inhibitors, none of these agents blocked the activity of PA in potentiating MPhi anti-MAC activity. Second, when PA was added to the in vitro anti-MAC bactericidal system consisting of either ROIs, reactive nitrogen intermediates (RNIs) or free fatty acid (FFA) molecules, which are the major MPhi antimicrobial effectors, PA inhibited the activity of ROIs and conversely potentiated the activity of RNIs; PA did not affect the activity of FFAs. Third, PA reduced mRNA expression of NADPH oxidase and beta-defensin-1 by MAC-infected MPhis, whilst neither cytosolic PLA(2) nor CAP37 mRNA expression was affected. Notably, inducible NOS and secretory PLA(2) mRNA expression was not detected for MAC-infected MPhis even when given PA treatment. These findings suggest that ROIs, RNIs, FFAs and beta-defensin-1 do not play important roles in the PA-induced potentiation of MPhi anti-MAC activity.
Tomioka
Haruaki
H
Department of Microbiology and Immunology, Shimane University School of Medicine, Enya-cho 89-1, Izumo, Shimane 693-8501, Japan. tomioka@med.shimane-u.ac.jp
Shimizu
Toshiaki
T
Tatano
Yutaka
Y
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology* / Q000502:physiology; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000472:pathogenicity*; D019255:NADPH Oxidases / Q000187:drug effects / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010848:Picolinic Acids / Q000494:pharmacology*; D011796:Quinacrine / Q000494:pharmacology; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D023083:beta-Defensins / Q000187:drug effects / Q000235:genetics
D000890:Anti-Infective Agents; C406407:DEFB1 protein, human; D004791:Enzyme Inhibitors; D010848:Picolinic Acids; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D023083:beta-Defensins; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D010741:Phospholipases A; D011796:Quinacrine; C030614:picolinic acid