, Volume 55, Issue 3, pp 119-127

Mechanisms of cell death induced by the neutrophil antimicrobial peptides α-defensins and LL-37

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Abstract.

Objective: The aim of this study was to investigate the mechanisms of cell death mediated by the antimicrobial peptides neutrophil defensins (human neutrophil peptides 1-3 [HNP1-3]) and LL-37.

Materials and methods: HNP1-3- and LL-37-mediated cell death was assessed in human lung epithelial cells and Jurkat T-cells in serum-free culture media.

Results: Both HNP1-3 and LL-37 induced cell death in Jurkat T-cells and A549 cells. HNP1-3 but not LL-37 induced caspase-3/-7 activity and caused cleavage of [ADP-ribose] polymerase (PARP) in Jurkat cells, while in A549 cells neither peptides induced caspase-3/-7 activation. Furthermore, both peptides increased mitochondrial cytochrome c release in A549 and Jurkat cells. Our observation that over-expression of the anti-apoptotic protein Bcl-2 in Jurkat cells did not affect HNP1-3- or LL-37-induced cell death indicates that antimicrobial peptide-induced cytochrome c release is not involved in peptide-induced cell death. Finally, in A549 cells and in primary bronchial epithelial cells, both HNP1-3 and LL-37 induced DNA breaks as demonstrated by increased TUNEL labelling.

Conclusions: The results from this study suggest that the antimicrobial peptides HNP1-3 and LL-37 induce cell death, which is associated with mitochondrial injury and mediated via different intracellular pathways.

Received 8 July 2005; returned for revision 21 October 2005; returned for final revision 8 December 2005; accepted by M. Parnham 14 December 2005
J. Aarbiou and G.S. Tjabringa contributed equally to this manuscript