Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to Accumulate Particles on Neutrophil Extracellular Traps
Neutrophils are involved in numerous immunological events. One mechanism of neutrophils to combat pathogens is the formation of neutrophil extracellular traps (NETs). Thereby, neutrophils use DNA fibers to form a meshwork of DNA and histones as well as several antimicrobial components to trap and ki...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01229/full |
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| author | Christina E. Galuska Christina E. Galuska Jan A. Dambon Jan A. Dambon Andrea Kühnle Kim F. Bornhöfft Gerlinde Prem Kristina Zlatina Kristina Zlatina Thomas Lütteke Sebastian P. Galuska Sebastian P. Galuska |
| author_facet | Christina E. Galuska Christina E. Galuska Jan A. Dambon Jan A. Dambon Andrea Kühnle Kim F. Bornhöfft Gerlinde Prem Kristina Zlatina Kristina Zlatina Thomas Lütteke Sebastian P. Galuska Sebastian P. Galuska |
| author_sort | Christina E. Galuska |
| collection | DOAJ |
| description | Neutrophils are involved in numerous immunological events. One mechanism of neutrophils to combat pathogens is the formation of neutrophil extracellular traps (NETs). Thereby, neutrophils use DNA fibers to form a meshwork of DNA and histones as well as several antimicrobial components to trap and kill invaders. However, the formation of NETs can lead to pathological conditions triggering among other things (e.g., sepsis or acute lung failure), which is mainly a consequence of the cytotoxic characteristics of accumulated extracellular histones. Interestingly, the carbohydrate polysialic acid represents a naturally occurring antagonist of the cytotoxic properties of extracellular histones. Inspired by polysialylated vesicles, we developed polysialylated nanoparticles. Since sialidases are frequently present in areas of NET formation, we protected the sensitive non-reducing end of these homopolymers. To this end, the terminal sialic acid residue of the non-reducing end was oxidized and directly coupled to nanoparticles. The covalently linked sialidase-resistant polysialic acid chains are still able to neutralize histone-mediated cytotoxicity and to initiate binding of these polysialylated particles to NET filaments. Furthermore, polysialylated fluorescent microspheres can be used as a bioanalytical tool to stain NET fibers. Thus, polySia chains might not only be a useful agent to reduce histone-mediated cytotoxicity but also an anchor to accumulate nanoparticles loaded with active substances in areas of NET formation. |
| first_indexed | 2024-12-22T02:10:56Z |
| format | Article |
| id | doaj.art-2a88db2c871a4998b2c6ed56d0d1c9f8 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T02:10:56Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2a88db2c871a4998b2c6ed56d0d1c9f82022-12-21T18:42:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-09-01810.3389/fimmu.2017.01229290932Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to Accumulate Particles on Neutrophil Extracellular TrapsChristina E. Galuska0Christina E. Galuska1Jan A. Dambon2Jan A. Dambon3Andrea Kühnle4Kim F. Bornhöfft5Gerlinde Prem6Kristina Zlatina7Kristina Zlatina8Thomas Lütteke9Sebastian P. Galuska10Sebastian P. Galuska11Institute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyFaculty of Medicine, Institute of Biochemistry, Justus-Liebig-University, Giessen, GermanyInstitute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyFaculty of Medicine, Institute of Biochemistry, Justus-Liebig-University, Giessen, GermanyInstitute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyInstitute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyFaculty of Medicine, Institute of Biochemistry, Justus-Liebig-University, Giessen, GermanyInstitute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyFaculty of Medicine, Institute of Biochemistry, Justus-Liebig-University, Giessen, GermanyInstitute of Veterinary Physiology and Biochemistry, Justus-Liebig-University, Giessen, GermanyInstitute of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, GermanyFaculty of Medicine, Institute of Biochemistry, Justus-Liebig-University, Giessen, GermanyNeutrophils are involved in numerous immunological events. One mechanism of neutrophils to combat pathogens is the formation of neutrophil extracellular traps (NETs). Thereby, neutrophils use DNA fibers to form a meshwork of DNA and histones as well as several antimicrobial components to trap and kill invaders. However, the formation of NETs can lead to pathological conditions triggering among other things (e.g., sepsis or acute lung failure), which is mainly a consequence of the cytotoxic characteristics of accumulated extracellular histones. Interestingly, the carbohydrate polysialic acid represents a naturally occurring antagonist of the cytotoxic properties of extracellular histones. Inspired by polysialylated vesicles, we developed polysialylated nanoparticles. Since sialidases are frequently present in areas of NET formation, we protected the sensitive non-reducing end of these homopolymers. To this end, the terminal sialic acid residue of the non-reducing end was oxidized and directly coupled to nanoparticles. The covalently linked sialidase-resistant polysialic acid chains are still able to neutralize histone-mediated cytotoxicity and to initiate binding of these polysialylated particles to NET filaments. Furthermore, polysialylated fluorescent microspheres can be used as a bioanalytical tool to stain NET fibers. Thus, polySia chains might not only be a useful agent to reduce histone-mediated cytotoxicity but also an anchor to accumulate nanoparticles loaded with active substances in areas of NET formation.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01229/fullneutrophil extracellular trapspolysialic acidnanoparticlehistoneslipopolysaccharides |
| spellingShingle | Christina E. Galuska Christina E. Galuska Jan A. Dambon Jan A. Dambon Andrea Kühnle Kim F. Bornhöfft Gerlinde Prem Kristina Zlatina Kristina Zlatina Thomas Lütteke Sebastian P. Galuska Sebastian P. Galuska Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to Accumulate Particles on Neutrophil Extracellular Traps Frontiers in Immunology neutrophil extracellular traps polysialic acid nanoparticle histones lipopolysaccharides |
| title | Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to Accumulate Particles on Neutrophil Extracellular Traps |
| title_full | Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to Accumulate Particles on Neutrophil Extracellular Traps |
| title_fullStr | Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to Accumulate Particles on Neutrophil Extracellular Traps |
| title_full_unstemmed | Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to Accumulate Particles on Neutrophil Extracellular Traps |
| title_short | Artificial Polysialic Acid Chains as Sialidase-Resistant Molecular-Anchors to Accumulate Particles on Neutrophil Extracellular Traps |
| title_sort | artificial polysialic acid chains as sialidase resistant molecular anchors to accumulate particles on neutrophil extracellular traps |
| topic | neutrophil extracellular traps polysialic acid nanoparticle histones lipopolysaccharides |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01229/full |
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