Neutrophils as a source of branched-chain, aromatic and positively charged free amino acids

Galkina, Svetlana I.; Федорова, Н. В.; Ksenofontov, Alexander L.; Stadnichuk, Vladimir I.; Baratova, Ludmila A.; Sud’ina, Galina F.

doi:10.1080/19336918.2018.1540903

Cited by 16 publications

(27 citation statements)

References 33 publications

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“…It is now well-accepted that antimicrobial peptides influence the regulation of inflammation by directly affecting immune cells and inducing the synthesis of immune response mediators [ 14 ]. Neutrophil cells are a rich source of cationic antimicrobial peptides [ 45 , 46 ] and positively charged free amino acids [ 47 ]. Synthetic cationic peptides modulate the uptake of CpG-ODNs, which enhances the immunostimulatory effects [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

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

Viryasova

Golenkina

Hianik

et al. 2021

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

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

Viryasova

Golenkina

Hianik

et al. 2021

IJMS

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“…In this study, tRNA transcription was low in the primary host cells (human granulocytes), but high in the cell lines, consistent with the observation that in humans, relatively few granulocytes are infected that support limited Ap growth and replication. Differentiated neutrophil granulocytes secrete branched-chain, aromatic and positively charged free amino acids upon adhesion to extracellular matrix (48), and inhibition of this response may increase availability to intracellular Ap (49). Evidence derived from in vitro studies of Ap and also in vivo with the related Anaplasma marginale indicates that microvascular endothelial cells are a nidus of infection (50)(51)(52), and these long-lived cells likely offer an environment supportive of growth and replication that requires import of amino acids.…”

Section: Discussionmentioning

confidence: 99%

Global Transcription Profiles of Anaplasma phagocytophilum at Key Stages of Infection in Tick and Human Cell Lines and Granulocytes

et al. 2020

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The incidence of human diseases caused by tick-borne pathogens is increasing but little is known about the molecular interactions between the agents and their vectors and hosts. Anaplasma phagocytophilum (Ap) is an obligate intracellular, tick-borne bacterium that causes granulocytic anaplasmosis in humans, dogs, sheep, and horses. In mammals, neutrophil granulocytes are a primary target of infection, and in ticks, Ap has been found in gut and salivary gland cells. To identify bacterial genes that enable Ap to invade and proliferate in human and tick cells, labeled mRNA from Ap bound to or replicating within human and tick cells (lines HL-60 and ISE6), and replicating in primary human granulocytes ex vivo, was hybridized to a custom tiling microarray containing probes representing the entire Ap genome. Probe signal values plotted over a map of the Ap genome revealed antisense transcripts and unannotated genes. Comparisons of transcript levels from each annotated gene between test conditions (e.g., Ap replicating in HL-60 vs. ISE6) identified those that were differentially transcribed, thereby highlighting genes associated with each condition. Bacteria replicating in HL-60 cells upregulated 122 genes compared to those in ISE6, including numerous p44 paralogs, five HGE-14 paralogs, and 32 hypothetical protein genes, of which 47% were predicted to be secreted or localized to the membrane. By comparison, 60% of genes upregulated in ISE6 encoded hypothetical proteins, 60% of which were predicted to be secreted or membrane associated. In granulocytes, Ap upregulated 120 genes compared to HL-60, 33% of them hypothetical and 43% of those predicted to encode secreted or membrane associated proteins. HL-60-grown bacteria binding to HL-60 cells barely responded transcriptionally, while ISE6-grown bacteria binding to ISE6 cells upregulated 48 genes. HL-60-grown bacteria, when incubated with ISE6 cells, upregulated the same genes that were upregulated by ISE6-grown bacteria exposed to uninfected ISE6. Hypothetical genes (constituting about 29% of Ap genes) played a disproportionate role in most infection scenarios, and particular sets of them were consistently upregulated in bacteria binding/entering both ISE6 and HL-60 cells. This suggested that the encoded proteins played central roles in establishing infection in ticks and humans.

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“…One of the limitations of this study is the lack of control of the subjects' diet and the evaluation of gut microbiota, and there is the ambiguity that the walking protocols in this study have affected the gut microbiota composition. Furthermore, neutrophils are also one of the secretive sources of arginine, ornithine, lysine, hydroxylysine, histidine (38). Galkina et al (38) found that insulin significantly stimulated the amount of secreted hydroxylysine, a metabolite of lysine, in neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, neutrophils are also one of the secretive sources of arginine, ornithine, lysine, hydroxylysine, histidine (38). Galkina et al (38) found that insulin significantly stimulated the amount of secreted hydroxylysine, a metabolite of lysine, in neutrophils. In addition, it has been reported that plasma concentrations of lysine positively associated with gestational diabetes mellitus through modifying IR and secretion (39).…”

Section: Discussionmentioning

confidence: 99%

“…In patients with diabetes or cardiovascular disease, the reduction of GABA commonly observed (40,41). Galkina et al (38) demonstrated that neutrophils secrete more ornithine than arginine, and this can contribute to the alteration of the PAAs content in patients with metabolic disorders. It is clear that there is a connection between obesity and neutrophils.…”

Section: Discussionmentioning

confidence: 99%

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The effect of eight-week walking program on plasma levels of amino acids in early/mid pubertal obese girls

Baghersalimi

Fathi

Kazemi

2019

Med. J. Islam. Republ. Iran

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Background: Altered circulating amino acids levels have been observed in metabolic disorders, like obesity, type-2 diabetes, and other insulin-resistant states. This study aimed to investigate the effect of 8-week walking on plasma amino acids (PAAs) in obese girls. Methods: This clinical trial study (IRCT20180928041160N1) was conducted on 32 early/mid pubertal obese girls which they divided into interval-walking (IWG, n=12), continuous-walking (CWG, n=11) and control (CG, n=9) groups. The walking program (3sessions/week for 8-weeks) consists of 30-min walking with 70-85%HRmax and 60-75%HRmax, respectively in the IWG (2-min walking and 1-min active rest) and CWG. The concentration of PAAs was measured at baseline and 72-hours after the last session in fasting state, using high-performance liquid chromatography. A repeated measures ANCOVA (group (3) * time (2)) with post hoc Bonferroni was used to analyze the data. Results: More the PAAs were not affected by interval or continuous walking training. A significant increase in lysine (p=0.003, 95%CI 24.08, 108.97) was observed only in the CG, and there was a significant difference between the CG and CWG (p=0.032). Global arginine bioavailability (GABA) significantly decreased in the CG (P<0.001, 95%CI-0.65,-0.21) and the IWG (p=0.004, 95%CI-0.60,-0.21). A significant increase in weight (p=0.043, 95%CI 0.27, 1.46), insulin (p=0.046, 95%CI-0.91, 9.01), and HOMA-IR (p=0.007, 95%CI 0.26, 2.63) were found only in the CG, and both insulin and HOMA-IR tended to decline in the CWG. Conclusion: Except for lysine and GABA, all groups roughly showed similar changes in more amino acids. Continuous-walking could improve the plasma level of lysine and GABA, which along with an improvement of fasting insulin levels and HOMA-IR.

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Neutrophils as a source of branched-chain, aromatic and positively charged free amino acids

Cited by 16 publications

References 33 publications

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

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

Global Transcription Profiles of Anaplasma phagocytophilum at Key Stages of Infection in Tick and Human Cell Lines and Granulocytes

The effect of eight-week walking program on plasma levels of amino acids in early/mid pubertal obese girls

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