Role of Nuclear Factor‐kappa B in the Activation of Alveolar Macrophages by Fungal Beta‐Glucans

Pneumocystis carinii (P. carinii) is a fungal pathogen that causes pneumonia in individuals with compromised immunity [l]. Betaglucans (8-glucans) are complex carbohydrates which represent major srructural cumponents of both fungal and plant cell walls. In addition to providing support in fungal cell walls, p-glucans also mediate important inflammatory responses through interactions with cognate glucan receptors on alveolar macrophages. We have recently demonstrated that particulate, endotoxin-free beta-glucan from the oppormnistic fungal pathogen P. carinii, as well as the phylogenetically related non-pathogenic fungus Succharomyces cerevisiue (S. cerevisiue), stimulate tumor necrosis factor alpha (TNFalpha) and macrophage inflammatory protein-2 release from alveolar macrophages [2]. Thus, p-glucan components of fungal cell walls participate directly in the inflammatory process that OCCUTS during the course of fungal pneumonia. The signal transduction mechanisms mediating alveolar macrophage activation and release of cytokines through stimulation with fungal p-glucan are not known. Recent studies indicate that the soluble p-glucan, Betafectin, activates the transcription factor nuclear factor kappa-B (NF-KB) in a murine monocytic cell line [3]. We hypothesized that activation of alveolar macrophages by insoluble particulate fungal p-glucan similarly occurs through activation of NF-KB.