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Pure mitochondrial DNA does not activate human neutrophils in vitro

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Abstract

Excessive activation of the innate immune system often leads to fatal consequences and can be considered as one of the phenoptotic events. After traumatic injury, various components of mitochondria are released into the circulation and stimulate myeloid cells of the innate immunity. Presumably, mitochondrial DNA (mtDNA) might activate immune cells (Zhang, Q., et al. (2010) Nature, 464, 104–107). In the present study, we investigated the role of mtDNA as a direct activator of human neutrophils, as well as a prognostic marker in patients with severe trauma. Quantitative determination of mtDNA in the plasma of these patients revealed its significant increase (p < 0.02) in the group of survivors compared to nonsurvivors. Highly purified mtDNA was not able to induce activation of human neutrophils, thus possibly indicating the existence of additional factor(s) ensuring the recognition of mtDNA as a damage-associated molecular pattern.

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Abbreviations

DAMP:

damage-associated molecular patterns

eDNA:

extracellular DNA

fMLP:

formyl-Met-Leu-Phe

ISS:

injury severity score

MMP9:

matrix metalloproteinase 9 (gelatinase)

MTD:

mitochondrial DAMP

mtDNA:

mitochondrial DNA

nDNA:

nuclear DNA

P-p38:

phosphorylated form of p38 MAPK

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Correspondence to R. A. Zinovkin.

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Published in Russian in Biokhimiya, 2015, Vol. 80, No. 5, pp. 746–753.

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Prikhodko, A.S., Shabanov, A.K., Zinovkina, L.A. et al. Pure mitochondrial DNA does not activate human neutrophils in vitro . Biochemistry Moscow 80, 629–635 (2015). https://doi.org/10.1134/S0006297915050168

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  • DOI: https://doi.org/10.1134/S0006297915050168

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