Candida albicans is an increasingly important fungal pathogen. Alveolar macrophages respond to fungal components such as zymosan by releasing arachidonic acid (AA) and AA metabolites. However, few studies have evaluated the effect of whole fungi on macrophage eicosanoid metabolism. We hypothesized that macrophages respond to C. albicans by releasing AA and generating AA metabolites as a consequence of interaction of mannose and β- glucan receptors with fungal cell wall components. [14C]AA-labeled rabbit alveolar macrophages released AA following stimulation with either live or heat-killed C. albicans. High-pressure liquid chromatography analysis revealed that 55% of the AA released was metabolized via cyclooxygenase and lipoxygenase pathways. The metabolites consisted of prostaglandin E2, prostaglandin F(2α), 6-ketoprostaglandin F(1α), thromboxane B2, and leukotrienes B4 and D4. We further examined the roles of α-mannan and β- glucan components of C. albicans in mediating these alterations of eicosanoid metabolism. Prior work in our laboratory has shown that soluble α-mannan and β-glucan inhibit macrophage mannose and β-glucan receptors, respectively. Incubation of alveolar macrophages with soluble α-mannan derived from C. albicans (1 mg/ml) resulted in 49.8% ± 2.6% inhibition of macrophage AA release during stimulation with intact C. albicans (P = 0.0001 versus control). Macrophage AA release in response to C. albicans was also inhibited to a significant but lesser degree by soluble β-glucan (36.2% ± 1.3%; P = 0.008 versus control). These results indicate that C. albicans stimulates macrophage AA metabolism and that these effects are partly mediated by α- mannan and β-glucan constituents of the fungus.
|Original language||English (US)|
|Number of pages||8|
|Journal||Infection and Immunity|
|State||Published - 1994|
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