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Polymers 2017, 9(12), 720;

Individual Impact of Distinct Polysialic Acid Chain Lengths on the Cytotoxicity of Histone H1, H2A, H2B, H3 and H4

Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University, Frankfurter Str. 100, 35392 Giessen, Germany
Author to whom correspondence should be addressed.
Current address: ITech Progress GmbH, Donnersbergweg 4, 67059 Ludwigshafen, Germany.
Received: 9 November 2017 / Revised: 11 December 2017 / Accepted: 13 December 2017 / Published: 16 December 2017
PDF [5837 KB, uploaded 16 December 2017]


Neutrophils are able to neutralize pathogens by phagocytosis, by the release of antimicrobial components, as well as by the formation of neutrophil extracellular traps (NETs). The latter possibility is a DNA-meshwork mainly consisting of highly concentrated extracellular histones, which are not only toxic for pathogens, but also for endogenous cells triggering several diseases. To reduce the negative outcomes initiated by extracellular histones, different approaches like antibodies against histones, proteases, and the polysaccharide polysialic acid (polySia) were discussed. We examined whether each of the individual histones is a binding partner of polySia, and analyzed their respective cytotoxicity in the presence of this linear homopolymer. Interestingly, all of the histones (H1, H2A, H2B, H3, and H4) seem to interact with α2,8-linked sialic acids. However, we observed strong differences regarding the required chain length of polySia to bind histone H1, H2A, H2B, H3, and H4. Moreover, distinct degrees of polymerization were necessary to act as a cytoprotective agent in the presence of the individual histones. In sum, the outlined results described polySia-based strategies to bind and/or to reduce the cytotoxicity of individual histones using distinct polySia chain length settings. View Full-Text
Keywords: polysialic acid; histones; neutrophil extracellular traps polysialic acid; histones; neutrophil extracellular traps

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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.; Lütteke, T.; Galuska, S.P. Individual Impact of Distinct Polysialic Acid Chain Lengths on the Cytotoxicity of Histone H1, H2A, H2B, H3 and H4. Polymers 2017, 9, 720.

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