(1-]3)-BETA-D-GLUCAN STIMULATES NITRIC-OXIDE GENERATION AND CYTOKINE MESSENGER-RNA EXPRESSION IN MACROPHAGES

Beta-glucans are known for their potent ability to induce nonspecific inflammatory reactions and are believed to pray a role in bioaerosol-i nduced respiratory symptoms seen in both occupational and residential environments. Here, the ability of a (1 --> 3)-beta-D-glucan (Curdlan) to stimulate nitric oxide generation and cytokine mRNA expression in rat alveolar macrophages (AMs) and the murine monocyte/macrophage cell line, RAW 264.7 was investigated. Exposure to (1 --> 3)-beta-D-glucan (20, 100 and 500 mu g/ml) induced a dose-dependent increase in the ex pression of inducible nitric oxide synthase mRNA and a release of nitr ic oxide into the culture medium in both rat AMs and RAW 263.7 cells. The mRNA expression of a number of other inflammatory mediators such a s interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha and c yclooxygenase-2 was also increased by the exposure to beta-glucan. The capability of (1 --> 3)-beta-D-glucan (500 mu g/ml) to induce mRNA sy nthesis of these various mediators were comparable to that of endotoxi n (1 mu g/ml). These results imply that (1 --> 3)-beta-D-glucan stimul ates the generation of nitric oxide, cytokines and prostaglandins in m acrophages and suggest the possibility that this may contribute to bio aerosol-induced respiratory symptoms seen in exposed individuals. (C) 1998 Elsevier Science B.V. All rights reserved.