Modification of neutrophil functions by naftifine.
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 degrees C for 30 min at 1-150 micrograms/ml) by 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.
Department of Dermatology, State University of New York-Health Science Center, Brooklyn 11203.
B A
BA
Solomon
W L
WL
Lee
S C
SC
Geen
K
K
Suntharalingam
S M
SM
Fikrig
A R
AR
Shalita
D000499:Allylamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008163:Luminescent Measurements; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D000499:Allylamine; C029178:naftifine