Am. J. Respir. Crit. Care Med., Vol 150, No. 4, 10 1994, 1123-1129.
Inhibition of lung immunity after intratracheal instillation of benzo(a)pyrene
LY Kong, MI Luster, D Dixon, J O'Grady and GJ Rosenthal
Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Benzo(a)pyrene (B(a)P) has been shown to suppress systemic immunity in
experimental animals, which may contribute to the growth of the
chemical-induced tumors. However, its effects on lung immunity after
inhalation, a common route for human exposure in urban areas, has not been
determined. These studies examine intratracheal B(a)P instillation on lung
natural killer (NK) cell activity, alveolar macrophage (AM) functions, and
susceptibility to tumor cell challenge in Fischer 344 (F- 344) rats. Adult
female F-344 rats were given a single intratracheal instillation of 0, 10,
20, or 40 mg B(a)P/kg body weight as a suspension, and lung NK cell
activity and AM functions were examined 7, 21, or 100 d later. Although
exposure to B(a)P did not alter cell recovery after lavage, histologic
changes were observed as evidenced by granulomatous inflammation and
squamous metaplasia. There was a slight but significant suppression of H2O2
and nitric oxide (NO) release from alveolar macrophages of treated animals
as well as NK cell activity from the lung digest. A marked suppression of
tumor necrosis factor- alpha (TNF alpha) and interleukin (IL-1) secretion
in LPS- and/or cytokine-activated alveolar macrophages occurred. The
suppressive effects were generally more severe on Day 7 after exposure than
on Days 21 or 100, although IL-1 remained depressed through Day 100 after
exposure. B(a)P exposure allowed for the increased growth of MADB106
metastatic tumor cells in the lung. These tumor cells were shown to be
highly sensitive to lysis by immune-mediators, including TNF
alpha.(ABSTRACT TRUNCATED AT 250 WORDS)
