title: In vitro generation of polysialylated cervical mucins by bacterial polysialyltransferases to counteract cytotoxicity of extracellular histones.
abstract: Neutrophil extracellular traps (NET) are formed against pathogens. However, various diseases are directly linked to this meshwork of DNA. The cytotoxic properties of extracellular histones especially seem to be an important trigger during these diseases. Furthermore, NET accumulation on implants is discussed to result in an impaired efficiency or failure, depending on the category of implant. Interestingly, mucins have been investigated as surface coatings potentially capable of reducing neutrophil adhesion. Similarly, polysialic acid was shown to inactivate the cytotoxic properties of extracellular histones. We wanted to combine the probability to decrease the adhesion of neutrophils using mucins with the capability of sialic acid polymers to counteract histone-mediated cytotoxicity. To this end, we elongate cervical mucins using bacterial polysialyltransferases. Subsequent cell-based experiments demonstrated the activity of elongated mucins against histone-mediated cytotoxicity. Thus, polysialylated mucins may represent a novel component to coat implants or to combat diseases with exaggerated NET formation.
authors.affiliation: Department of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.|Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Sebastian P
authors.initials: SP
authors.lastname: Galuska
authors.affiliation: Department of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.|Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Christina E
authors.initials: CE
authors.lastname: Galuska
authors.affiliation: UCD Veterinary Sciences Centre, University College Dublin, Belfield, Ireland.
authors.forename: Tharmala
authors.initials: T
authors.lastname: Tharmalingam
authors.affiliation: Department of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.|Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Zlatina
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Prem
authors.affiliation: Department of Reproductive Biology, Leibniz Institute for Farm Animal Biology (FBN), Dummerstorf, Germany.|Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: Farzali C O
authors.initials: FCO
authors.lastname: Husejnov
authors.affiliation: Dublin-Oxford Glycobiology Laboratory, NIBRT - The National Institute for Bioprocessing Research and Training, Blackrock Co., Dublin, Ireland.
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.affiliation: Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Willie F
authors.initials: WF
authors.lastname: Vann
authors.affiliation: UCD Veterinary Sciences Centre, University College Dublin, Belfield, Ireland.
authors.forename: Colm
authors.initials: C
authors.lastname: Reid
authors.affiliation: Food and Drug Administration, Silver Spring, MD, USA.
authors.forename: Justine
authors.initials: J
authors.lastname: Vionnet
authors.affiliation: UCD Veterinary Sciences Centre, University College Dublin, Belfield, Ireland.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Gallagher
authors.affiliation: UCD Veterinary Sciences Centre, University College Dublin, Belfield, Ireland.
authors.forename: Faye A
authors.initials: FA
authors.lastname: Carrington
authors.affiliation: UCD Veterinary Sciences Centre, University College Dublin, Belfield, Ireland.
authors.forename: Sarah-Louise
authors.initials: SL
authors.lastname: Hassett
authors.affiliation: UCD Veterinary Sciences Centre, University College Dublin, Belfield, Ireland.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Carrington
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D002417:Cattle; D002448:Cell Adhesion; D002460:Cell Line; D002582:Cervix Mucus / Q000737:chemistry*; D002645:Chickens; D004971:Estrus; D065206:Extracellular Traps / Q000502:physiology*; D005260:Female; D006657:Histones / Q000037:antagonists & inhibitors* / Q000502:physiology / Q000633:toxicity; D066298:In Vitro Techniques; D009077:Mucins / Q000378:metabolism*; D009345:Neisseria meningitidis / Q000201:enzymology*; D009504:Neutrophils / Q000166:cytology; D012794:Sialic Acids / Q000378:metabolism*; D012799:Sialyltransferases / Q000378:metabolism*; D013552:Swine
chemical_list: D001426:Bacterial Proteins; D006657:Histones; D009077:Mucins; D012794:Sialic Acids; C021319:polysialic acid; D012799:Sialyltransferases
keywords: extracellular histones; implants; mucin; neutrophil extracellular traps; polysialic acid