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.
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
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
Rights and permissions
About this article
Cite this article
Aarbiou, J., Tjabringa, G.S., Verhoosel, R.M. et al. Mechanisms of cell death induced by the neutrophil antimicrobial peptides α-defensins and LL-37. Inflamm. res. 55, 119–127 (2006). https://doi.org/10.1007/s00011-005-0062-9
Issue Date:
DOI: https://doi.org/10.1007/s00011-005-0062-9