Biphasic effects of cyclosporin A on formyl-methionyl-leucyl- phenylalanine stimulated responses in HL-60 cells differentiated into neutrophils

摘要

The immunosuppressive drug cyclosphorin A(CsA) depresses neutrophil oxidative burst which may lead to an increased susceptibility to infection in transplant patients. Using specific CsA analogues we investigated the mechanism of inhibition of the oxidative burst and evaluated short and long-tem effects of CsA on dimethylsulphoxide-differentiated HL-60 neutrophils. A biphasic pattern was observed: 1 4 h pre-treatment with CsA (1 μM)diminished the fMLP induced [Ca~2+]c rise, reactive oxygen species (ROS) production, and β-glucuronidase release by about 40/100, whereas a 20 h pre-treatment increased these responses by about 1.5 fold.