The Pro-Oxidant Effect of Class A CpG ODNs on Human Neutrophils Includes Both Non-Specific Stimulation of ROS Production and Structurally Determined Induction of NO Synthesis

Synthetic CpG oligonucleotides are promising components of immunomodulatory drugs for the treatment and prophylaxis infectious diseases, cancers, allergies. Phosphorothioate modification stabilizes these compounds, contributing to achievement a clinical effect, but at same time changes their properties. We used diffusible fluorescent dye dihydroethidium non-diffusible 6-carboxy-2′,7′dihydrochlorofluorescein diacetate cytochrome c probes demonstrate that it is phosphorothioate backbones determine pronounced nonspecific pro-oxidant effect ODN on neutrophils. At time, as was shown using diaminofluorescein diacetate, potentiation nitric oxide synthesis in leucocytes by class A strictly depends presence motifs palindromic “hairpin”. The results obtained will contribute more complete understanding physiological action therapeutic agents based synthetic oligonucleotides.