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The antimicrobial peptide LL-37 facilitates the formation of neutrophil extracellular traps

Neumann, Ariane LU ; Berends, Evelien T. M. ; Nerlich, Andreas ; Molhoek, E. Margo ; Gallo, Richard L. ; Meerloo, Timo ; Nizet, Victor ; Naim, Hassan Y. and von Köckritz-Blickwede, Maren (2014) In The Biochemical journal 464(1). p.3-11
Abstract

NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. During formation of NETs, the nuclear membrane is disrupted by an as-yet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence microscopy revealed that 5 μM LL-37 significantly facilitated NET formation by primary human blood-derived neutrophils alone, in the presence of the classical chemical NET inducer PMA or in the presence of Staphylococcus aureus. Parallel assays with a random LL-37 fragment library indicated that the NET induction is mediated by the hydrophobic character of the peptide. The trans-localization of... (More)

NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. During formation of NETs, the nuclear membrane is disrupted by an as-yet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence microscopy revealed that 5 μM LL-37 significantly facilitated NET formation by primary human blood-derived neutrophils alone, in the presence of the classical chemical NET inducer PMA or in the presence of Staphylococcus aureus. Parallel assays with a random LL-37 fragment library indicated that the NET induction is mediated by the hydrophobic character of the peptide. The trans-localization of LL-37 towards the nucleus and the disruption of the nuclear membrane were visualized using confocal fluorescence microscopy. In conclusion, the present study demonstrates a novel role for LL-37 in the formation of NETs.

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author
; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
keywords
Amino Acid Sequence, Animals, Cathelicidins, Extracellular Traps, Humans, Male, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Neutrophils, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
in
The Biochemical journal
volume
464
issue
1
pages
9 pages
publisher
Portland Press
external identifiers
  • scopus:84908453654
  • pmid:25181554
ISSN
0264-6021
DOI
10.1042/BJ20140778
language
English
LU publication?
no
id
cbd66a6f-2967-4537-a20c-aeac98c2631d
date added to LUP
2017-09-19 12:16:07
date last changed
2024-02-13 04:21:26
@article{cbd66a6f-2967-4537-a20c-aeac98c2631d,
  abstract     = {{<p>NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. During formation of NETs, the nuclear membrane is disrupted by an as-yet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence microscopy revealed that 5 μM LL-37 significantly facilitated NET formation by primary human blood-derived neutrophils alone, in the presence of the classical chemical NET inducer PMA or in the presence of Staphylococcus aureus. Parallel assays with a random LL-37 fragment library indicated that the NET induction is mediated by the hydrophobic character of the peptide. The trans-localization of LL-37 towards the nucleus and the disruption of the nuclear membrane were visualized using confocal fluorescence microscopy. In conclusion, the present study demonstrates a novel role for LL-37 in the formation of NETs.</p>}},
  author       = {{Neumann, Ariane and Berends, Evelien T. M. and Nerlich, Andreas and Molhoek, E. Margo and Gallo, Richard L. and Meerloo, Timo and Nizet, Victor and Naim, Hassan Y. and von Köckritz-Blickwede, Maren}},
  issn         = {{0264-6021}},
  keywords     = {{Amino Acid Sequence; Animals; Cathelicidins; Extracellular Traps; Humans; Male; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Neutrophils; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{1}},
  pages        = {{3--11}},
  publisher    = {{Portland Press}},
  series       = {{The Biochemical journal}},
  title        = {{The antimicrobial peptide LL-37 facilitates the formation of neutrophil extracellular traps}},
  url          = {{http://dx.doi.org/10.1042/BJ20140778}},
  doi          = {{10.1042/BJ20140778}},
  volume       = {{464}},
  year         = {{2014}},
}