Priming of Human Neutrophils Is Necessary for Their Activation by Extracellular DNA

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A. S. Prikhodko¹, M. V. Vitushkina², L. A. Zinovkina¹, E. N. Popova³, and R. A. Zinovkin^2,3*

¹Lomonosov Moscow State University, Faculty of Bioengineering and Bioinformatics, 119991 Moscow, Russia

²Lomonosov Moscow State University, Faculty of Biology, 119991 Moscow, Russia; E-mail: roman.zinovkin@gmail.com

³Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received February 19, 2016; Revision received March 13, 2016

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Extracellular plasma DNA is thought to act as a damage-associated molecular pattern causing activation of immune cells. However, purified preparations of mitochondrial and nuclear DNA were unable to induce neutrophil activation in vitro. Thus, we examined whether granulocyte-macrophage colony-stimulating factor (GM-CSF) acting as a neutrophil priming agent can promote the activation of neutrophils by different types of extracellular DNA. GM-CSF pretreatment greatly increased p38 MAPK phosphorylation and promoted CD11b/CD66b expression in human neutrophils treated with mitochondrial and, to a lesser extent, with nuclear DNA. Our experiments clearly indicate that GM-CSF-induced priming of human neutrophils is necessary for their subsequent activation by extracellular DNA.

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KEY WORDS: neutrophil activation, GM-CSF, extracellular DNA, nuclear DNA, mitochondrial DNA

DOI: 10.1134/S0006297916060079

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