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Studies on citrullinated LL-37: detection in human airways, antibacterial effects and biophysical properties
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.ORCID-id: 0000-0003-4464-1769
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Antal upphovsmän: 132020 (Engelska)Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 2376Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Arginine residues of the antimicrobial peptide LL-37 can be citrullinated by peptidyl arginine deiminases, which reduce the positive charge of the peptide. Notably, citrullinated LL-37 has not yet been detected in human samples. In addition, functional and biophysical properties of citrullinated LL-37 are not fully explored. The aim of this study was to detect citrullinated LL-37 in human bronchoalveolar lavage (BAL) fluid and to determine antibacterial and biophysical properties of citrullinated LL-37. BAL fluid was obtained from healthy human volunteers after intra-bronchial exposure to lipopolysaccharide. Synthetic peptides were used for bacterial killing assays, transmission electron microscopy, isothermal titration calorimetry, mass-spectrometry and circular dichroism. Using targeted proteomics, we were able to detect both native and citrullinated LL-37 in BAL fluid. The citrullinated peptide did not kill Escherichia coli nor lysed human red blood cells. Both peptides had similar α-helical secondary structures but citrullinated LL-37 was more stable at higher temperatures, as shown by circular dichroism. In conclusion, citrullinated LL-37 is present in the human airways and citrullination impaired bacterial killing, indicating that a net positive charge is important for antibacterial and membrane lysing effects. It is possible that citrullination serves as a homeostatic regulator of AMP-function by alteration of key functions.

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2020. Vol. 10, nr 1, artikel-id 2376
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Farmaceutiska vetenskaper
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URN: urn:nbn:se:su:diva-185673DOI: 10.1038/s41598-020-59071-7ISI: 000560368700001PubMedID: 32047184OAI: oai:DiVA.org:su-185673DiVA, id: diva2:1472361
Tillgänglig från: 2020-10-01 Skapad: 2020-10-01 Senast uppdaterad: 2022-09-15Bibliografiskt granskad

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Wallin, CeciliaBalhuizen, Melanie D.Végvári, ÁkosGräslund, Astrid

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Wallin, CeciliaBalhuizen, Melanie D.Végvári, ÁkosGräslund, Astrid
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