Biochemical Journal 2014-11-15

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

Index: Biochem. J. 464(1) , 3-11, (2014)

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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.