Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides
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 a...
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doaj-64165e0383a040f2b3825202cc29ced12021-04-28T23:00:16ZengMDPI AGPathogens2076-08172021-04-011053053010.3390/pathogens10050530Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing OligonucleotidesEkaterina A. Golenkina0Svetlana I. Galkina1Nina G. Dolinnaya2Evgenii A. Arifulin3Yulia M. Romanova4Galina F. Sud’ina5Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaDepartment of Chemistry, Lomonosov Moscow State University, 119991 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaGamaleya National Research Centre of Epidemiology and Microbiology, 123098 Moscow, RussiaBelozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, RussiaMimicking 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.https://www.mdpi.com/2076-0817/10/5/530neutrophilmodified oligonucleotidesreactive oxygen speciesCpG oligonucleotidesapoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ekaterina A. Golenkina Svetlana I. Galkina Nina G. Dolinnaya Evgenii A. Arifulin Yulia M. Romanova Galina F. Sud’ina |
spellingShingle |
Ekaterina A. Golenkina Svetlana I. Galkina Nina G. Dolinnaya Evgenii A. Arifulin Yulia M. Romanova Galina F. Sud’ina Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides Pathogens neutrophil modified oligonucleotides reactive oxygen species CpG oligonucleotides apoptosis |
author_facet |
Ekaterina A. Golenkina Svetlana I. Galkina Nina G. Dolinnaya Evgenii A. Arifulin Yulia M. Romanova Galina F. Sud’ina |
author_sort |
Ekaterina A. Golenkina |
title |
Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides |
title_short |
Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides |
title_full |
Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides |
title_fullStr |
Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides |
title_full_unstemmed |
Synthetic Hexanucleotides as a Tool to Overcome Excessive Neutrophil Activation Caused by CpG-Containing Oligonucleotides |
title_sort |
synthetic hexanucleotides as a tool to overcome excessive neutrophil activation caused by cpg-containing oligonucleotides |
publisher |
MDPI AG |
series |
Pathogens |
issn |
2076-0817 |
publishDate |
2021-04-01 |
description |
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. |
topic |
neutrophil modified oligonucleotides reactive oxygen species CpG oligonucleotides apoptosis |
url |
https://www.mdpi.com/2076-0817/10/5/530 |
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