Stimulation of human neutrophil degranulation by mefloquine.
The effect of the antimalarial drug mefloquine on human neutrophil degranulation, chemiluminescence, superoxide production and viability was examined in vitro. Mefloquine was found to significantly stimulate the release of lysozyme, beta-glucuronidase and myeloperoxide at a concentration of 10 micrograms/ml (2.5 X 10(-5) M) without loss of cell viability. At 40 micrograms/ml mefloquine (1 X 10(-4) M) cell viability was significantly decreased. Mefloquine at 10 micrograms/ml also significantly increased the release of lysozyme and beta-glucuronidase but not myeloperoxidase when neutrophils were stimulated with opsonized zymosan. At a lower zymosan concentration myeloperoxidase release was also increased. Enzyme activity was not directly stimulated by mefloquine. Mefloquine at 10 micrograms/ml significantly increased luminol-dependent chemiluminescence but significantly inhibited lucigenin-dependent chemiluminescence when neutrophils were stimulated with opsonized zymosan. Under these conditions superoxide release, measured by cytochrome c reduction, was inhibited to a lesser degree. These results are discussed with reference to our previous report that mefloquine inhibits the neutrophil iodination reaction [Immunology 58: 125-130, 1986] and the use of mefloquine as an anti-inflammatory drug.
Bates
E J
EJ
University Department of Paediatrics, Adelaide Children's Hospital, South Australia.
Ferrante
A
A
D002470:Cell Survival / Q000187:drug effects; D003594:Cytoplasmic Granules / Q000187:drug effects*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D008163:Luminescent Measurements; D015767:Mefloquine; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000648:ultrastructure*; D011804:Quinolines / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D011804:Quinolines; D013481:Superoxides; D009113:Muramidase; D005966:Glucuronidase; D015767:Mefloquine