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Int. J. Mol. Sci. 2018, 19(6), 1679;

Polysialic Acid in Human Plasma Can Compensate the Cytotoxicity of Histones

Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Friedrichstr. 24, 35392 Giessen, Germany
Institute of Anatomy and Cell Biology, Justus-Liebig-University, Aulweg 123, 35385 Giessen, Germany
Author to whom correspondence should be addressed.
Received: 7 May 2018 / Revised: 28 May 2018 / Accepted: 29 May 2018 / Published: 5 June 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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The innate immune system has numerous mechanisms to fight against pathogens, including the formation of neutrophil extracellular traps (NETs). By spreading out chromatin, antimicrobial peptides and enzymes, neutrophils efficiently trap pathogens like bacteria and facilitate their elimination. During this process, high concentrations of extracellular histones can be reached. Several researchers have demonstrated that the cytotoxic characteristics of these histones can trigger diseases like sepsis. Interestingly, the carbohydrate polysialic acid (polySia) can bind histones and reduce histone-mediated cytotoxicity in a chain length-dependent manner. In the present study, we examined the chain length of polySia in plasma and tested its ability to decrease the cytotoxic characteristics of extracellular histones. Remarkably, we detected polySia not only in the soluble fraction of plasma, but also on enriched extracellular vesicles (EVs). Chain length analysis revealed that polySia chains originating from human plasma can consists of more than 40 sialic acid residues and show a cytoprotective effect against extracellular histones. Intriguingly, polySia is not only present in human plasma but also in fish and other branches of vertebrates. Thus, polySia is a physiological element in plasma and may represent a natural buffer for extracellular histones. View Full-Text
Keywords: polysialic acid; plasma; histone; neutrophil extracellular traps; NETs polysialic acid; plasma; histone; neutrophil extracellular traps; NETs

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zlatina, K.; Saftenberger, M.; Kühnle, A.; Galuska, C.E.; Gärtner, U.; Rebl, A.; Oster, M.; Vernunft, A.; Galuska, S.P. Polysialic Acid in Human Plasma Can Compensate the Cytotoxicity of Histones. Int. J. Mol. Sci. 2018, 19, 1679.

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