Effects of gold-chloroquine complexes on respiratory burst of polymorphonuclear leukocytes.
The effects of gold-chloroquine derivatives with the formula [Au(PR3)(CQ)]PF6 (where R = Ph (1), Et or Me) on the superoxide anion production by human neutrophils (PMNs, polymorphonuclear cells) were investigated. When these complexes (0.1-3 mumol/l) were added to PMNs prior to the activators formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristate acetate (PMA), they inhibited isoluminol-horseradish peroxidase-dependent chemiluminescence (CLisol). The inhibition was a direct result of effects on PMNs since chemiluminescence in the cell-free system (horseradish peroxidase-hydrogen peroxidase-isoluminol) was not affected. The above mentioned concentrations of the complexes did not show in vitro toxicity on the cells. On the other hand, when 1 mumol/l of complex 1 was added to cells after stimulation, the chemiluminescence of PMNs stimulated by PMA was inhibited, but not the chemiluminescence stimulated by fMLP. The gold-chloroquine binding was essential for the referred activity as chemiluminescence was not influenced by the precursors chloroquine (CAS 54-05-7) and AuCl(PPh3). Furthermore, the extent of inhibition of chemiluminescence in PMNs activated by PMA did not increase with the duration of preincubation in presence of 1 mumol/l of 1. Extensive washing of cells after preincubation with 1 mumol/l of 1 reversed the aforementioned inhibition. All these results show that the gold-chloroquine binding can lead to compounds with specific properties that could make them useful in the treatment of some inflammatory diseases.
Navarro
Maribel
M
Chemistry Center, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela. mnavarro@ivic.ve
Vásquez
Flor
F
Velásquez
Mait
M
Medina
Rafael
R
Reggio
Ronald
R
Fraile
German
G
D000255:Adenosine Triphosphate / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002474:Cell-Free System; D002738:Chloroquine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006046:Gold / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006046:Gold; D002738:Chloroquine; D000255:Adenosine Triphosphate; D013755:Tetradecanoylphorbol Acetate