A. V. Parshikov, А. V. Stefanov
Institute of Pharmacology and Toxicology, Academy of Medical Sciences of Ukraine, Kyiv;
Reactive oxygen and nitrogen intermediates are key factors in inflammatory response and antitumoral activity of macrophages. Free and liposomal N-acetylglucosaminyl-N-acetylmuramyl-L-alanyl-D-isoglutamine influence on murine macrophages ability to generate superoxide and nitric oxide were studied. The cells pretreated by GMDP increased superoxide generation in response to secondary stimuli (phorbol ether, lipopolysaccharide, zymosan). Encapsulation in the egg phosphatidylcholine liposomes enhanced cell sensitivity to priming effect of GMDP. The presence of liposomes (up to 0.5 mg/ml) in the medium inhibited superoxide release by macrophages probably due to participation of NO as redox-active metabolite. GMDP (up to 50 µg/ml) alone as well as GMDP with LPS treatment stimulated nitric oxide synthesis by macrophages. Liposomal GMDP at lower concentrations (up to 0.02 µg/ml) enhanced macrophage response to LPS. In contrast, NO-synthetic activity of LPS-stimulated cells decreased along with the increase of liposomal GMDP concentration (up to 0.5 µg/ml). The conditions for effective use of liposomal GMDP in immunotherapy are discussed.
Key words: macrophages, glucosaminylmuramyl dipeptide, liposomes, superoxide, nitric oxide.
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