Enhanced phagocytosis and intracellular killing of Pityrosporum ovale by human neutrophils after exposure to ketoconazole is correlated to changes of the yeast cell surface.
In seborrhoeic dermatitis an inflammatory response occurs secondary to large numbers of Pityrosporum yeasts appearing within and beneath the epidermis. To study the interaction between human neutrophils and P. ovale and any immunomodulating effect of antifungal agents, the yeast was exposed to ketoconazole and then incorporated into neutrophil monolayer assays. Phagocytosis was complement dependent and reached a maximum after 40 min. Ketoconazole at 25, 50 and 100 mg l-1 had no significant effect on phagocytosis of P. ovale. However, when yeast cells were pretreated with ketoconazole for 2 h before exposure to the phagocyte monolayer there was a significant enhancement of phagocytosis with increasing drug concentration. Intracellular killing of P. ovale was assessed by methylene blue dye exclusion. In the absence of ketoconazole, 5% of intracellular yeast cells were killed following internalization for 2 h. Pretreatment of yeast cells with ketoconazole at 10 and 100 mg l-1 for 2 h prior to ingestion significantly increased intracellular killing to a maximum of 23%. This study demonstrates that yeast cells of P. ovale are readily ingested by human neutrophils by a complement dependent process. Phagocytosis is enhanced if the organism is exposed to ketoconazole before opsonisation and ingestion. The inability of neutrophils to kill P. ovale is modulated in the presence of therapeutic concentrations of ketoconazole.
Richardson
M D
MD
Department of Dermatology, Anderson College, University of Glasgow, UK.
Shankland
G S
GS
D002478:Cells, Cultured; D012628:Dermatitis, Seborrheic / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology*; D008290:Malassezia / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010587:Phagocytosis
D007654:Ketoconazole