The Potential of Telomeric G-Quadruplexes Containing Modified Oligoguanosine Overhangs in Activation of Bacterial Phagocytosis and Leukotriene Synthesis in Human Neutrophils

摘要: Human neutrophils are the first line of defense against bacterial and viral infections. They eliminate pathogens through phagocytosis, which activate 5-lipoxygenase (5-LOX) pathway resulting in synthesis leukotrienes. Using HPLC analysis, flow cytometry, other biochemical methods, we studied effect synthetic oligodeoxyribonucleotides (ODNs) able to fold into G-quadruplex structures on main functions neutrophils. Designed ODNs contained four human telomere TTAGGG repeats (G4) including those with phosphorothioate oligoguanosines attached end(s) core. Just modified analogues G4 was shown more actively than parent ODN penetrate cells, improve phagocytosis Salmonella typhimurium bacteria, affect 5-LOX activation, cytosol calcium ion level, oxidative status As evident from CD UV spectroscopy data, presence flanking sequence leads dramatic changes topology. While folds a single antiparallel structure, two folded forms have been identified solutions ODNs: dominant, stable parallel. Thus, both secondary structure their ability cytoplasm cells important for activation neutrophil cellular effects. Our results offer new clues understanding role ligands regulation integral processes creating antimicrobial agents generation.