In vitro generation of polysialylated cervical mucins by bacterial polysialyltransferases to counteract cytotoxicity of extracellular histones. (26th April 2017)

• Record Type: Journal Article
• Authors: Galuska, Sebastian P.; Galuska, Christina E.; Tharmalingam, Tharmala; Zlatina, Kristina; Prem, Gerlinde; Husejnov, Farzali C. O.; Rudd, Pauline M.; Vann, Willie F.; Reid, Colm; Vionnet, Justine; Gallagher, Mary E.; Carrington, Faye A.; Hassett, Sarah‐Louise; Carrington, Stephen D.
• Is Part Of: FEBS journal. Volume 284:Number 11(2017)
• Page Start: 1688
• Page End: 1699
• Publication Date: 2017-04-26
• Subjects: extracellular histones -- implants -- mucin -- neutrophil extracellular traps -- polysialic acid; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.14073
• Languages: English
• ISSNs: 1742-464X

Abstract

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. Abstract : Sialylated glycans of cervical mucins were elongated with bacterial polysialyltransferases . The in vitro generated polysialylated mucins could be used to combat the cytotoxicity of extracellular histones. Thus, polysialylated mucins might be a useful tool to combat neutrophil extracellular traps‐mediated cell damages, which are triggered by extracellular histones.