Suppression of polymorphonuclear leukocyte bactericidal activity by suramin.
Suramin is a polyanionic compound with potent antineoplastic properties. Because polymorphonuclear leukocytes (PMNs) are a crucial component of host defenses against bacteria and fungi, the effects of suramin on PMN function were studied in vitro. PMNs from healthy donors were incubated with concentrations of suramin of 1 to 1,000 micrograms/ml (within and exceeding the therapeutic range) for 30 min, and PMN functional parameters were subsequently assessed. Suramin had no effect on viability, chemotaxis to N-formylmethionyl leucyl phenylalanine, phagocytosis of Candida albicans, or superoxide anion production in response to phorbol myristate acetate and formylmethionyl leucyl phenylalanine. Fungicidal activity against C. albicans blastoconidia was unaffected at a suramin concentration of < 500 micrograms/ml, whereas at higher concentrations a slight suppression was observed (P = 0.04). Bactericidal activity against Staphylococcus aureus was significantly suppressed by concentrations of > or = 100 micrograms/ml (P < 0.01). Phagocytosis of S. aureus was also significantly impaired at > or = 10 micrograms/ml (P < 0.05). The presence of 10% human serum during pretreatment did not abrogate the suramin-induced suppression of bactericidal activity. Treatment of PMNs with granulocyte colony-stimulating factor (4,000 U/ml) for 30 min prior to the addition of suramin (250 micrograms/ml) improved the bactericidal defect (P = 0.02). The PMN functional impairment may be related to increased susceptibility to bacterial infections, and granulocyte colony-stimulating factor may improve the defect.
Roilides
E
E
Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892.
Paschalides
P
P
Freifeld
A
A
Pizzo
P A
PA
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000633:toxicity; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013481:Superoxides / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology* / Q000633:toxicity
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D013498:Suramin