Fluconazole and platelet microbicidal protein inhibit Candida adherence to platelets in vitro.
Adherence to vascular endothelium is considered an essential step in the pathogenesis of hematogenously disseminated candidiasis. Platelets have been shown to promote Candida adherence to vascular endothelium in vitro. In contrast, recent studies indicate that platelets may also play a role in the primary host defense against endovascular infection by secretion of alpha granule-derived platelet microbicidal protein (PMP), which possesses both bactericidal and fungicidal activities as well as antiadherence properties. We examined the influences of PMP and the antifungal agent fluconazole on the adherence of Candida albicans to rabbit platelets, as measured by quantitative flow cytometry. In the absence of PMP and fluconazole, adherence of C. albicans to platelets was rapid (complete within 1 min), saturable, and reversible. Following 2 h of exposure to fluconazole at 10x the MIC, platelet binding of C. albicans was substantially reduced (mean reduction, 32.1%; P = 0.08). Similarly, exposure of C. albicans to PMP (range, 0.5 to 5 micrograms/ml) for 2 h (but not 30 min) significantly reduced candidal adherence to platelets 43.1 to 62.1%; (reduction range, P < 0.05). Moreover, exposure of C. albicans to PMP (5 micrograms/ml for 30 min) and then fluconazole (10x the MIC for 2 h) further decreased candidal adherence to platelets in comparison with the adherence after exposure to either agent alone (mean reduction, 57.2%; P = 0.02 and 0.05, respectively). These data demonstrate that PMP and fluconazole individually reduce the ability of C. albicans to bind to platelets in vitro and that the antiadherence activities of fluconazole are augmented by PMP.
Yeaman
M R
MR
Department of Medicine, St. John's Cardiovascular Research Center, Los Angeles County-Harbor University of California, Los Angeles Medical Center, Torrance 90509.
Sullam
P M
PM
Dazin
P F
PF
Ghannoum
M A
MA
Edwards
J E
JE
Bayer
A S
AS
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D001798:Blood Proteins / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D018925:Chemokines; D005434:Flow Cytometry; D015725:Fluconazole / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D066298:In Vitro Techniques; D011817:Rabbits; D001620:beta-Thromboglobulin
D000890:Anti-Infective Agents; D001798:Blood Proteins; D018925:Chemokines; D005456:Fluorescent Dyes; C061615:PPBP protein, human; D001620:beta-Thromboglobulin; C077150:platelet microbicidal protein, Oryctolagus cuniculus; D015725:Fluconazole