Chloroquine and hydroxychloroquine inhibit multiple sites in metabolic pathways leading to neutrophil superoxide release.
The effect of chloroquine and hydroxychloroquine on human neutrophil polymorph superoxide (O2-) production stimulated either by opsonized zymosan, phorbol myristate acetate or fluoride was examined in vitro. Both drugs inhibited the response to all 3 stimuli in a dose and time dependent fashion. Inhibition of zymosan stimulated O2- release was only attributable in a minor degree to inhibition of expression of surface receptors (MO-1), and appeared to be mainly due to inhibitory effects on more distal components of the activation pathway. Possible mechanisms for the inhibition of fluoride and phorbol ester stimulated O2- release are discussed in the light of current understanding of metabolic pathways of neutrophil polymorph activation.
Hurst
N P
NP
Combined Royal Adelaide and Queen Elizabeth Hospital Rheumatology Unit, Woodville, South Australia.
French
J K
JK
Gorjatschko
L
L
Betts
W H
WH
D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D005459:Fluorides / Q000037:antagonists & inhibitors; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011951:Receptors, Complement / Q000187:drug effects; D017463:Receptors, Complement 3b; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015054:Zymosan / Q000037:antagonists & inhibitors
D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D013481:Superoxides; D006886:Hydroxychloroquine; D002738:Chloroquine; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate; D005459:Fluorides