C, or aurasperone-C is not proved. The spore toxin may exert its effect through its Background -The fungus Aspergillus ability to diffuse rapidly into the lung lining fumigatus, whose spores are present fluid, diminish the macrophage oxidative ubiquitously in the air, causes a range of burst, and play a part in allowing A diseases in the human lung. A small mofumigatus to persist in the lung and manilecular weight (<10 kD) heat stable toxin fest its well known pathogenic effects. released from the spores of clinical and (Thorax 1997;52:796-801) environmental isolates of A fumigatus within minutes of deposition in aqueous Keywords: Aspergillus fumigatus, macrophage, gliotoxin, solution has previously been described. A fumagillin, helvolic acid, fumigaclavine-C, aurasperone-C. key effect of the toxin was to inhibit the oxidative burst of macrophages as measured by superoxide anion release. It was The fungus Aspergillus fumigatus is commonly hypothesised that the toxin was one of the found in the environment, its usual habitat commonly found A fumigatus hyphal tox-being dead or decaying organic matter. The ins such as gliotoxin. This inhibitor may fungus causes many human lung diseases 1 2 and be an important factor which allows the a major factor in determining the pathogenicity fungus to colonise the lung.of the fungus is the size of the spores (around Methods -The spore derived inhibitor was 3 m in diameter) which are present ubishown to inhibit the respiratory burst of quitously in the air. Mullins et al 3 have shown rat alveolar macrophages, as measured that many more spores of A fumigatus are presby the generation of superoxide anion. ent in the lungs at necropsy than would be Samples of the spore diffusate were subject anticipated from their presence in the air. The to reversed phase high performance spores therefore appear to have some survival liquid chromatography (HPLC), thin layer advantage in the human lung over other spores. chromatography (TLC), high perform-The survival rate of spores of A fumigatus in ance thin layer chromatography rabbit lung is greater than that of control spores (HPTLC), or organic extraction followed of a similar size. 4 Several factors have been by TLC or HPLC to identify the presence suggested as contributing to the pathogenesis of gliotoxin, fumagillin, helvolic acid, of A fumigatus. fumigaclavine-C, and aurasperone-C.Proteases, including a 32 kD chymotrypsinCommercially obtained preparations of like protease present on spores and hyphae, the toxins gliotoxin, fumagillin and hel-have been shown to reduce cell spreading 5 and volic acid and extracts enriched for promote detachment of cultured cells. 6 7 A low fumigaclavine-C and aurasperone-C were molecular weight component from the spore used as internal and external standards surface has been shown to inhibit the spreading and in the respiratory burst meas-and chemotaxis of macrophages, 5 to inhibit urements.the macrophage respiratory burst, 8 and also to Results -Gliotoxin, fumagillin, helvolic prevent phagocyt...