Modification of neutrophil functions by naftifine

1365-2133

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Naftifine (NF), a topical antimycotic agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. NF inhibits human polymorphonuclear leucocyte (PMN) chemotaxis. Following stimulation with zymosan-activated serum. 85–97% of the PMNs exhibited detectable membrane ruffling and polarity. In contrast, NF-treated PMNs did not exhibit such chemotactic factor-induced shape changes. We also analysed the effect of NF on PMN superoxide anion (O2−) and chemiluminescence (CL) production, as a measure of respiratory burst activity. Stimulation of PMNs pre-incubated with NF (37°C for 30 min at 1–150 μg/ml) hy FMLP, PMA and zymosan resulted in a dose-dependent inhibition in PMN CL. Doses of NF which depressed chemotaxis, inhibited CL and diminished O2− production in a statistically significant manner (P〈0.05–0.001). In conclusion, NF alters membrane-related responses in PMNs, and this alteration may be associated with a change in PMN morphology. Binding of NF to PMN membrane sterol, with a subsequent alteration in membrane configuration, is the most likely cause of the inhibition of PMN function. The data collectively document biochemical and morphological differences between control and NF-treated PMNs as determined by stimulus-specific CL and O2− generation and membrane shape change. Such differences may account, in part, for its efficacy in inflammatory fungal skin diseases.

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