Mechanisms of destruction of Aspergillus fumigatus hyphae mediated by human monocytes.

Normal monocytes attached to and destroyed Aspergillus hyphae by morphologic and metabolic criteria. Inhibition by anaerobiosis, azide, cyanide, halide-free conditions, catalase, histidine, and tryptophan suggested mediation of hyphal damage primarily through the myeloperoxidase system. However, myeloperoxidase-independent oxidative or nonoxidative mechanisms appeared active in hyphal damage by monocytes from patients with myeloperoxidase deficiency or chronic granulomatous disease (CGD). Moreover, hyphae were damaged by lysates and granule-enriched fractions of monocytes from patients with CGD, whereas comparable fractions of normal monocytes were active only with added halide and H2O2. Hyphal damage by both whole monocytes and granule-enriched fractions from patients with CGD was inhibited by polyanions, a result suggesting that cationic proteins may be involved. Hyphal damage by normal monocytes or monocytes from patients with CGD was inhibited by cells that lacked antihyphal activity (chlorpromazine-treated normal neutrophils or neutrophils from patients with CGD, respectively). This effect may predispose patients with CGD to chronic, invasive aspergillosis.