Nitric oxide synthesis in murine peritoneal macrophages by fungal beta-glucans

Fungal beta-glucans have abilities to induce NO (nitric oxide) synthesis by macrophages in vivo, and the intensity of NO synthesis significantly varied dependent on the structure of beta-glucans. The molecular mechanism of NO synthesis by beta-glucans, however, has not been clarified in detail. To determine beta-glucan-mediated NO production, we used various beta-glucans (SPG-OH, GRN; Grifolan, SSG, OL-2, ZYM; zymosan A and ZYC; zymocel), which could enhance NO synthesis in vivo, and stimulated peritoneal macrophages (MPs) in vitro in the presence of interferon-gamma (IFN-gamma). Using recombinant cytokines, a minimum concentration of the cytokines for NO induction was about 20 mg/ml in the presence of IFN-gamma under the experimental conditions. Of beta-glucans tested, only SPG-OH and GRN produced high concentrations of IL-6 in the culture supernatants. SSG also induced NO synthesis in vitro, but concentrations of inflammatory cytokines were low even in the presence of IFN-gamma. In addition, there are some beta-glucans which could induce NO synthesis in vivo but not in vitro (OL-2, ZYM, ZYC). These findings suggested that NO productivity of beta-glucans in vivo is regulated by several mechanisms.