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


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.
Aarbiou
J
J
Department of Pulmonology, C3-P, Leiden University Medical Center, P.O. Box 9600, 2300, RC Leiden, The Netherlands.
Tjabringa
G S
GS
Verhoosel
R M
RM
Ninaber
D K
DK
White
S R
SR
Peltenburg
L T C
LT
Rabe
K F
KF
Hiemstra
P S
PS