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

• Published in: International journal of molecular sciences Vol. 22; no. 5; p. 2671
• Main Authors: Viryasova, Galina M, Golenkina, Ekaterina A, Hianik, Tibor, Soshnikova, Nataliya V, Dolinnaya, Nina G, Gaponova, Tatjana V, Romanova, Yulia M, Sud'ina, Galina F
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.03.2021; MDPI
• Subjects: acoustic method; Adjuvants; Antiinfectives and antibacterials; Arachidonate 5-lipoxygenase; Arachidonate 5-Lipoxygenase - metabolism; Bacteria; Benzamides - pharmacology; Biological activity; Calcium - metabolism; CpG Islands; Deoxyribonucleic acid; DNA; Enzyme Activation - drug effects; Humans; Inflammation; Inhibitors; Kinetics; Langmuir isotherm; Leucine; Leukocytes (neutrophilic); leukotriene; Leukotrienes - biosynthesis; Lipoxygenase; Liquid oxygen; LRR11; Metabolites; neutrophil; Neutrophils; Neutrophils - drug effects; Neutrophils - metabolism; oligodeoxyribonucleotides; Oligodeoxyribonucleotides - chemical synthesis; Oligodeoxyribonucleotides - pharmacology; Opsonin Proteins; Pathogens; Peptide Fragments - pharmacology; Peptides; Phagocytosis; Physiology; Reactive Oxygen Species - metabolism; Receptor for Advanced Glycation End Products - antagonists & inhibitors; Salmonella; Salmonella typhimurium; TLR9 protein; Toll-Like Receptor 9 - physiology; Toll-like receptors; acoustic method; LRR11; oligodeoxyribonucleotides; neutrophil; leukotriene; Langmuir isotherm
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22052671

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 . 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.