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Article

Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils

1
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
2
Department of Nuclear Physics and Biophysics, Comenius University, Mlynska dolina F1, 842 48 Bratislava, Slovakia
3
Institute of Gene Biology, Department of Eukaryotic Transcription Factors, Russian Academy of Sciences, Vavilov Str. 34/5, 119334 Moscow, Russia
4
Department of Chemistry, Lomonosov Moscow State University, 119234 Moscow, Russia
5
National Research Center for Hematology, Russia Federation Ministry of Public Health, 125167 Moscow, Russia
6
Gamaleya National Research Centre of Epidemiology and Microbiology, 123098 Moscow, Russia
*
Author to whom correspondence should be addressed.
Academic Editor: Yoshiro Kobayashi
Int. J. Mol. Sci. 2021, 22(5), 2671; https://doi.org/10.3390/ijms22052671
Received: 22 January 2021 / Revised: 26 February 2021 / Accepted: 1 March 2021 / Published: 6 March 2021
(This article belongs to the Special Issue Current Trends of Neutrophil Biology 2.0)
Neutrophil-mediated innate host defense mechanisms include pathogen elimination through bacterial phagocytosis, which activates the 5-lipoxygenase (5-LOX) product synthesis. Here, we studied the effect of synthetic oligodeoxyribonucleotides (ODNs), which mimic the receptor-recognized sites of bacterial (CpG-ODNs) and genomic (G-rich ODNs) DNAs released from the inflammatory area, on the neutrophil functions after cell stimulation with Salmonella typhimurium. A possible mechanism for ODN recognition by Toll-like receptor 9 (TLR9) and RAGE receptor has been proposed. We found for the first time that the combination of the magic peptide LRR11 from the leucine-rich repeat (LRR) of TLR9 with the CpG-ODNs modulates the uptake and signaling from ODNs, in particular, dramatically stimulates 5-LOX pathway. Using thickness shear mode acoustic method, we confirmed the specific binding of CpG-ODNs, but not G-rich ODN, to LRR11. The RAGE receptor has been shown to play an important role in promoting ODN uptake. Thus, FPS-ZM1, a high-affinity RAGE inhibitor, suppresses the synthesis of 5-LOX products and reduces the uptake of ODNs by neutrophils; the inhibitor effect being abolished by the addition of LRR11. The results obtained revealed that the studied peptide-ODN complexes possess high biological activity and can be promising for the development of effective vaccine adjuvants and antimicrobial therapeutics. View Full-Text
Keywords: neutrophil; leukotriene; oligodeoxyribonucleotides; LRR11; acoustic method; Langmuir isotherm neutrophil; leukotriene; oligodeoxyribonucleotides; LRR11; acoustic method; Langmuir isotherm
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MDPI and ACS Style

Viryasova, G.M.; Golenkina, E.A.; Hianik, T.; Soshnikova, N.V.; Dolinnaya, N.G.; Gaponova, T.V.; Romanova, Y.M.; Sud’ina, G.F. Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils. Int. J. Mol. Sci. 2021, 22, 2671. https://doi.org/10.3390/ijms22052671

AMA Style

Viryasova GM, Golenkina EA, Hianik T, Soshnikova NV, Dolinnaya NG, Gaponova TV, Romanova YM, Sud’ina GF. Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils. International Journal of Molecular Sciences. 2021; 22(5):2671. https://doi.org/10.3390/ijms22052671

Chicago/Turabian Style

Viryasova, Galina M.; Golenkina, Ekaterina A.; Hianik, Tibor; Soshnikova, Nataliya V.; Dolinnaya, Nina G.; Gaponova, Tatjana V.; Romanova, Yulia M.; Sud’ina, Galina F. 2021. "Magic Peptide: Unique Properties of the LRR11 Peptide in the Activation of Leukotriene Synthesis in Human Neutrophils" Int. J. Mol. Sci. 22, no. 5: 2671. https://doi.org/10.3390/ijms22052671

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