Abstract
Antimicrobial peptides are small molecular weight proteins with a large antibacterial spectrum. They can reach high local concentrations in tissues with active inflammation, being largely produced by immunocompetent cells. However, their effect on eukaryotic cells is still unclear. We have, therefore, studied three structurally different antimicrobial peptides (cecropin P1, PRβ39 and NKβlysin) for their cytotoxic effects on blood mononuclear cells. None of the antimicrobial peptides tested exhibited significant cytotoxic effect on resting lymphocytes isolated either from peripheral blood or from the spleen with the exception of high concentrations (ten times higher than IC100 for Escherichia coli) of NKβlysin. Activated lymphocytes were, however, more sensitive to the cytotoxic effect of the antimicrobial peptides. Both activated Tβcells and Bβcells were dose dependent sensitive to NKβlysin while only activated Bβcells but not activated Tβcells were sensitive to PRβ39. Cecropin did not exhibit any cytotoxic effect on activated lymphocytes either. By using several cell lines (3B6, K562, U932 and ELβ4) we were able to show that NKβlysin has a broad necrotic effect while PRβ39 has a cell specific apoptotic effect dependent on the specifically cellular uptake. In conclusion we show here that antimicrobial peptides are not cytotoxic for the resting eukaryotic cells but can be cytotoxic on activated immune cells through distinct mechanisms of cell death. Copyright Β© 2009 European Peptide Society and John Wiley & Sons, Ltd.