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Inflammation Research

, Volume 55, Issue 3, pp 119–127 | Cite as

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

  • J. Aarbiou
  • G. S. Tjabringa
  • R. M. Verhoosel
  • D. K. Ninaber
  • S. R. White
  • L. T. C. Peltenburg
  • K. F. Rabe
  • P. S. Hiemstra
Original Research Papers

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.

Keywords.

Antimicrobial peptides Defensins Cathelicidins Cytotoxicity Caspases 

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Copyright information

© Birkhäuser Verlag, Basel 2006

Authors and Affiliations

  • J. Aarbiou
    • 1
  • G. S. Tjabringa
    • 1
  • R. M. Verhoosel
    • 1
  • D. K. Ninaber
    • 1
  • S. R. White
    • 3
  • L. T. C. Peltenburg
    • 2
    • 4
  • K. F. Rabe
    • 1
  • P. S. Hiemstra
    • 1
  1. 1.Department of Pulmonology, C3-PLeiden University Medical CenterRC LeidenThe Netherlands
  2. 2.Clinical OncologyLeiden University Medical CenterRC LeidenThe Netherlands
  3. 3.Section of Pulmonary and Critical Care Medicine, Department of Medicine, Division of Biological SciencesThe University of ChicagoChicagoUSA
  4. 4.Crucell Holland B.V.LeidenThe Netherlands

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