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Pathogens. 2021 Apr 28;10(5). doi: 10.3390/pathogens10050530.

Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides.

Pathogens (Basel, Switzerland)

Ekaterina A Golenkina, Svetlana I Galkina, Nina G Dolinnaya, Evgenii A Arifulin, Yulia M Romanova, Galina F Sud'ina

Affiliations

  1. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
  2. Department of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia.
  3. Gamaleya National Research Centre of Epidemiology and Microbiology, 123098 Moscow, Russia.

PMID: 33924760 PMCID: PMC8146577 DOI: 10.3390/pathogens10050530

Abstract

Mimicking bacterial DNA, synthetic CpG-containing oligodeoxyribonucleotides (CpG-ODNs) have a powerful immunomodulatory potential. Their practical application is mainly associated with the production of vaccines, where they are used as adjuvants, as well as in local antimicrobial therapy. CpG-ODNs act on a wide variety of immune cells, including neutrophilic granulocytes. On the one hand, the stimulatory effect provides both the direct implementation of their antimicrobial and fungicidal mechanisms, and an avalanche-like strengthening of the immune signal due to interaction with other participants in the immune process. On the other hand, hyperactivation of neutrophilic granulocytes can have negative consequences. In particular, the formation of unreasonably high amounts of reactive oxygen species leads to tissue damages and, as a consequence, a spontaneous aggravation and prolongation of the inflammatory process. Under physiological conditions, a large number of DNA fragments are present in inflammation foci: both of microbial and self-tissue origin. We investigated effects of several short modified hexanucleotides on the main indicators of neutrophil activation, as well as their influence on the immunomodulatory activity of known synthetic CpG-ODNs. The results obtained show that short oligonucleotides partially inhibit the prooxidant effect of synthetic CpG-ODNs without significantly affecting the ability of the latter to overcome bacteria-induced pro-survival effects on neutrophilic granulocytes.

Keywords: CpG oligonucleotides; apoptosis; modified oligonucleotides; neutrophil; reactive oxygen species

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