The cytotoxic effects of the anti-bacterial peptides on leukocytes

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, PR-39 and NK-lysin) 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 NK-lysin. Activated lymphocytes were, however, more sensitive to the cytotoxic effect of the antimicrobial peptides. Both activated T-cells and B-cells were dose dependent sensitive to NK-lysin while only activated B-cells but not activated T-cells were sensitive to PR-39. Cecropin did not exhibit any cytotoxic effect on activated lymphocytes either. By using several cell lines (3B6, K562, U932 and EL-4) we were able to show that NK-lysin has a broad necrotic effect while PR-39 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.