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Nitric oxide is an important antimicrobial mechanism of phagocytes from mice and rats, but in the case of human phagocytes, secretion is still controversial. We investigated whether nitric oxide is involved in the killing of Aspergillus fumigatus conidia by human or murine pulmonary alveolar macrophages. Stimulation of the macrophages with gamma interferon and Escherichia coli lipopolysaccharide had no effect on fungicidal activity against conidia in vitro, with or without the addition of tetrahydrobiopterin. Killing of conidia (means +/- standard deviations) by murine or human alveolar macrophages, before and after stimulation, was 44% +/- 13% and 49% +/- 12% (P = 0.34) and 24% +/- 5% and 29% +/- 10% (P = 0.20), respectively. Fungicidal activity was unaltered in the presence of the competitive inhibitor NG-monomethyl L-arginine, and nitrite was undetectable in cell supernatants. Peritoneal macrophages from B6C3F1 mice produced 18 mumol of nitrite per 10(6) cells in 18 h. In conclusion, nitric oxide does not appear to be involved in the fungicidal activity of murine or human alveolar macrophages against A. fumigatus conidia.

Lack of involvement of nitric oxide in killing of Aspergillus fumigatus conidia by pulmonary alveolar macrophages