LACK OF INVOLVEMENT OF NITRIC-OXIDE IN KILLING OF ASPERGILLUS-FUMIGATUS CONIDIA BY PULMONARY ALVEOLAR MACROPHAGES

Nitric oxide is an important antimicrobial mechanism of phagocytes fro m mice and rats, but in the case of human phagocytes, secretion is sti ll controversial. We investigated whether nitric oxide is involved in the killing of Aspergillus fumigatus conidia by human or murine pulmon ary alveolar macrophages. Stimulation of the macrophages with gamma in terferon and Escherichia coli lipopolysaccharide had no effect on fung icidal activity against conidia in vitro, with or without the addition of tetrahydrobiopterin. Killing of conidia (means +/- standard deviat ions) by murine or human alveolar macrophages, before and after stimul ation, was 44% +/- 13% and 49% +/- 12% (P = 0.34) and 24% +/- 5% and 2 9% +/- 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 macrop hages from B6C3F1 mice produced 18 mu mol of nitrite per 10(6) cells i n 18 h. In conclusion, nitric oxide does not appear to be involved in the fungicidal activity of murine or human alveolar macrophages agains t A. fumigatus conidia.