Aclacinomycin, an anti-leukemic anthracycline, impairs human neutrophil functions.
The effects of aclacinomycin, an anti-leukemic anthracycline, on human neutrophil functions were investigated. The release of superoxide (O2-) in neutrophils stimulated by opsonized zymosan, myristate, or phorbol myristate acetate was inhibited by aclacinomycin in a dose- and time-dependent manner. The phagocytosis of yeast particles and oil droplets, and membrane potential changes stimulated by phorbol myristate acetate were also inhibited by aclacinomycin. On the other hand, the O2(-)-producing enzyme (NADPH oxidase) in the particulate fraction prepared from myristate-stimulated neutrophils was not affected by aclacinomycin. When high concentrations of aclacinomycin (10-100 micrograms/ml) were employed, significant inhibition of O2- release, phagocytosis, and membrane potential changes was observed within 5 min. Phagocytic activity was also inhibited when neutrophils were preincubated for 13 h at 37 degrees C with a low concentration (40 ng/ml) of aclacinomycin, which could be obtained by intravenous administration of 20 mg aclacinomycin. Myristate-induced O2- release was not impaired by cytosine arabinoside (2-800 micrograms/ml), vincristine (0.1-100 micrograms/ml), adriamycin (25-100 micrograms/ml), or daunomycin (5-75 micrograms/ml) when the cells were preincubated with these drugs for 5 min at 37 degrees C. These findings suggest that aclacinomycin inhibits the respiratory burst by impairing the activating system of NADPH oxidase and phagocytic activity.
Katoh
M
M
First Department of Internal Medicine, School of Medicine, Toho University, Tokyo, Japan.
Fukuhara
Y
Y
Chiba
T
T
Shirai
T
T
Kitagawa
S
S
Kakinuma
K
K
D015250:Aclarubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; C011157:aclacinomycins; D013481:Superoxides; D015250:Aclarubicin; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases