title: The antimicrobial peptide LL-37 facilitates the formation of neutrophil extracellular traps.
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 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.
authors.affiliation: *Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Ariane
authors.initials: A
authors.lastname: Neumann
authors.affiliation: †Medical Microbiology, University Medical Center, 3584 CX Utrecht, The Netherlands.
authors.forename: Evelien T M
authors.initials: ET
authors.lastname: Berends
authors.affiliation: ‡Institute of Microbiology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Nerlich
authors.affiliation: §TNO Earth, Environmental and Life Sciences, Department CBRN protection, 2280 AA Rijswijk, The Netherlands.
authors.forename: E Margo
authors.initials: EM
authors.lastname: Molhoek
authors.affiliation: ∥Division of Dermatology, Department of Medicine, University of California San Diego, San Diego, CA 92122, U.S.A.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
authors.affiliation: ¶Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, U.S.A.
authors.forename: Timo
authors.initials: T
authors.lastname: Meerloo
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.affiliation: *Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Hassan Y
authors.initials: HY
authors.lastname: Naim
authors.affiliation: *Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000235:genetics / Q000494:pharmacology*; D065206:Extracellular Traps / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins