INFLUENCE OF NIFEDIPINE ON PLASMA-MEMBRANE FLUIDITY AND OXIDATIVE BURST OF POLYMORPHONUCLEAR LEUKOCYTES

It has been demonstrated that the calcium antagonist nifedipine inhibi ts the reactive oxygen species (ROS) production by polymorphonuclear l eucocytes (PMNLs) activated with phorbol myristate acetate (PMA), but the mechanism underlying this effect is still unknown. In the present study we investigated the influence of nifedipine on the PMNL plasma m embrane using (4-trimethylaminophenyl)-6-phenyl-1,3,5,hexatriene (TMA- DPH) fluorescence polarization (P) and on PMA- and N-formyl-methionyl- leucyl-phenylalanine (FMLP)-induced ROS production, measured by lumino l-dependent chemiluminescence (CL). The plasma membrane fluidity of un treated PMNLs, expressed as P, was 0.371 +/- 0.008. After preincubatio n of 15 min, nifedipine induced a significant change in P values only at a concentration of 10(-4) M (P=0.00018). After preincubation of 60 min significant changes in P values were also observed at concentratio ns of 10(-6) M (P=0.023) and 10(-7) M (P=0.023). PMA-induced ROS produ ction by PMNLs was markedly inhibited by nifedipine. Nifedipine also d etermined a striking change in the FMLP-induced CL response, character ized by both an overall inhibition of PMNL activity and a modification of the kinetics of the oxidative burst (rapid increase in ROS product ion followed by a pronounced drop in the PMNL response). Such a patter n was found at concentrations of 10(-4) M (preincubation time: 15 min) , 10(-6) M and 10(-7) M (preincubation time: 60 min). These findings i ndicate that nifedipine directly interacts with the PMNLs by inducing a marked decrease in plasma membrane fluidity and an inhibition of the oxidative burst.