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.
The antimicrobial peptide LL-37 facilitates the formation of neutrophil extracellular traps
Ariane Neumann, Evelien T. M. Berends, Andreas Nerlich, E. Margo Molhoek, Richard L. Gallo, Timo Meerloo, Victor Nizet, Hassan Y. Naim, Maren von Köckritz-Blickwede; The antimicrobial peptide LL-37 facilitates the formation of neutrophil extracellular traps. Biochem J 15 November 2014; 464 (1): 3–11. doi: https://doi.org/10.1042/BJ20140778
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