Influence of nifedipine on plasma membrane fluidity and oxidative burst of polymorphonuclear leucocytes.
It has been demonstrated that the calcium antagonist nifedipine inhibits the reactive oxygen species (ROS) production by polymorphonuclear leucocytes (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 membrane using 1-(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 luminol-dependent chemiluminescence (CL). The plasma membrane fluidity of untreated PMNLs, expressed as P, was 0.371 +/- 0.008. After preincubation 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 concentrations of 10(-6) M (P = 0.023) and 10(-7) M (P = 0.023). PMA-induced ROS production by PMNLs was markedly inhibited by nifedipine. Nifedipine also determined a striking change in the FMLP-induced CL response, characterized by both an overall inhibition of PMNL activity and a modification of the kinetics of the oxidative burst (rapid increase in ROS production followed by a pronounced drop in the PMNL response). Such a pattern 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 indicate that nifedipine directly interacts with the PMNLs by inducing a marked decrease in plasma membrane fluidity and an inhibition of the oxidative burst.
Grassi
W
W
Department of Rheumatology, University of Ancona, Ospedale A. Murri, Jesi, Italy.
Serretti
R
R
Core
P
P
Muti
S
S
Cervini
C
C
D005454:Fluorescence Polarization; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008560:Membrane Fluidity / Q000187:drug effects*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors; D014969:Xanthine Oxidase / Q000032:analysis
D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D014969:Xanthine Oxidase; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate