Effects of fungal β‐glucan and interferon‐γ on the secretory functions of murine alveolar macrophages

We investigated the effect of a fungal component, soluble β‐glucan, on secretory functions of murine alveolar macrophages (AMs) in vitro. Stimulation by β‐glucan (500 μg/mL) or interferon‐γ (IFN‐γ; 100 U/mL) alone had a slight effect on AM functions, but when AMs were incubated together with β‐glucan and IFN‐γ, the production and secretion of some immune mediators, such as nitric oxide, interleukin‐1 (IL‐1), IL‐6, and tumor necrosis factor‐α (TNF‐α), were markedly augmented. This combined effect of β‐glucan and IFN‐γ was based on a priming effect of IFN‐γ, because prestimulation with IFN‐γ followed by β‐glucan induced high nitric oxide production of AMs, but reversal of the sequence of treatments had only a slight effect. We also found that preincubation of AMs with IFN‐γ enhanced the binding of fluorescein‐labeled β‐glucan on the AM surface, and this increased binding was abrogated to the control level by the addition of three species of soluble unlabeled (1→3)‐β‐d‐glucans but not by soluble α‐glucan. These data imply that the priming effect of IFN‐γ on the AM response to β‐glucan was dependent, at least in part, on the enhancement of β‐glucan specific binding sites on the AM surface. It was suggested that IFN‐γ is one of the principal factors controlling the pulmonary immune system against both severe fungal infection and inflammation via AM activation at the alveoli.