Comparative roles of free fatty acids with reactive nitrogen intermediates and reactive oxygen intermediates in expression of the anti-microbial activity of macrophages againstMycobacterium tuberculosis

Abstract

SUMMARYWe assessed the role of free fatty acids (FFA) in the expression of the activity of macrophages against Mycobacterium tuberculosis in relation to the roles of two major anti-microbial effectors, reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI). Intracellular growth of M. tuberculosis residing inside macrophages was accelerated by treatments of macrophages with either quinacrine (phospholipase A 2 (PLA 2 ) inhibitor), arachidonyl trifuloromethylketone (type IV cytosolic PLA 2 inhibitor), N G -monomethyl-l-arginine (nitric oxide synthase inhibitor), and superoxide dismutase plus catalase (ROI scavengers). In addition, M. tuberculosis-infected macrophages produced and/or secreted these effectors sequentially in the order ROI (0±3 h), FFA (0±48 h), and RNI (3 to at least 72 h). Notably, membranous FFA (arachidonic acid) of macrophages translocated to M. tuberculosis residing in the phagosomes of macrophages in phagocytic ability-and PLA 2 -dependent fashions during cultivation after M. tuberculosis infection. FFA, RNI and H 2 O 2 -mediated halogenation system (H 2 O 2 -halogenation system) displayed strong activity against M. tuberculosis in cell-free systems, while ROI alone exerted no such effects. Combinations of`FFA 1 RNI' and`RNI 1 H 2 O 2 -halogenation system' exhibited synergistic and additive effects against M. tuberculosis, respectively, while`FFA 1 H 2 O 2 -halogenation system' had an antagonistic effect. Moreover, a sequential attack of FFA followed by RNI exerted synergistic activity against M. tuberculosis. Since M. tuberculosis-infected macrophages showed simultaneous production of RNI with FFA secretion for relatively long periods (approx. 45 h) and prolonged RNI production was seen thereafter, RNI in combination with FFA appear to play critical roles in the manifestation of the activity of macrophages against M. tuberculosis.

Immunobiochemical Study of Host During Malaria Infection via Nitric Oxide Pathway after Modulation by Lipopolysaccharide and Dexamethasone in Mice Model

“…Chem., 9 (5): 260-268, 2015 C o n t r o l There are several stimuli were reported to activate the immune system, especially to induce cytokines and NO (Gharavi et al, 2011). Nitrogen oxide has complex and diverse functions in physiological and pathophysiological phenomena; accumulated evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases (Akaki et al, 2000). Studies have shown that severe cases of malaria are accompanied by increased iNOS activity and the subsequent production of NO (Bryk et al, 2000).…”

VAKSINASI BCG MENINGKATKAN AKTIVITAS FAGOSITOSIS DAN SEKRESI REACTIVE OXYGEN INTERMEDIATE (ROI) PADA MAKROFAG PERITONEUM KUCING YANG DIINFEKSI DENGAN Mycobacterium tuberculosis

“…Peningkatan aktivitas makrofag dalam sekresi ROI yang mencapai puncaknya pada minggu kedua setelah infeksi, juga didukung dengan hasil penelitian berikutnya yang menunjukkan bahwa pada minggu kedua setelah infeksi selain aktivitas sekresi ROI yang mencapai puncak, aktivitas makrofag dalam fagositosis juga mencapai puncaknya pada waktu yang sama (24). Reactive oxygen intermediate merupakan produk oksidatif makrofag yang memainkan peranan penting dalam mekanisme pembunuhan M. tuberculosis, yang aktivitasnya diinduksi oleh sitokin IFN-γ dan TNF-α (25,26). Kemampuan BCG dalam menstimulasi respon imun seluler khususnya dalam mekanisme sebagai efektor oksidatif pada mencit telah banyak dilaporkan.…”

Mutation in alkylhydroperoxidase D gene dramatically decreases persistence of <i>Mycobacterium bovis</i> bacillus calmette-guerin in infected macrophage

“…[3] In this situation, produced peroxynitrite (ONOO-) and other reactive nitrogen and oxygen intermediates plays an important role in host defense against the invading bacteria. [4,5] Consequently, many bacterial pathogens have evolved protective mechanisms against reactive oxygen and nitrogen intermediates. [6] On the other hand, it has been cleared that mutation in the catalase-peroxidase katG gene of M. tuberculosis resulted in resistance to isoniazid [7] and mutation in the ß avoprotein mono-oxygenase etaA gene, resulted in resistance to ethionamide.…”