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Elevated TNF‐α and inducible nitric oxide production by alveolar macrophages after exposure to a nitrite inhalant
Author(s) -
Soderberg Lee S. F.,
Chang Louis W.,
Barnett John B.
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.60.4.459
Subject(s) - nitric oxide , nitrite , tumor necrosis factor alpha , inhalation , immunology , lung , macrophage , alveolar macrophage , pulmonary alveolus , inhalation exposure , pathology , biology , medicine , respiratory disease , endocrinology , in vitro , biochemistry , anatomy , ecology , nitrate
Abuse of nitrite inhalants, widespread among male homosexuals, has been identified by epidemiological studies as an independent risk factor for AIDS and for Kaposi's sarcoma. Subchronic exposure of mice to inhaled isobutyl nitrite was previously found to impair the tumoricidal activity of peritoneal macrophages. Because inhalants would be expected to have the greatest effects on cells in the lung, alveolar macrophages from exposed mice were examined in this study. Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 min/day for 14 days. Following this treatment, the lungs of exposed mice had large increases in ccllularity, both in the alveolar septa and within the alveoli. Broncho alveolar lavages also contained increased numbers of cells. Alveolar macrophages collected from treated mice had increased tumoricidal activity compared with controls and produced higher levels of inducible nitric oxide and tumor necrosis factor‐α (TNF‐α), The frequency of alveolar cells secreting TNF‐α was increased ninefold in mice exposed to the inhalant. Cell influx into the lung, as indicated by the presence of red blood cells in lung lavages, was evident after only a single 45‐min exposure to inhaled isobutyl nitrite at doses as low as 300 ppm. J. Leukoc. Biol . 60: 459–464; 1996.