Ozone-induced release of cytokines and fibronectin by alveolar macrophages and airway epithelial cells.
Acute exposure of animals and humans to ozone results in decrements in lung function, development of airway hyperreactivity, inflammation, edema, damage to pulmonary cells, and production of several compounds with tissue damaging, fibrinogenic or fibrotic potential. The contribution of airway epithelial cells and alveolar macrophages to these processes is unclear. In this study we have directly exposed human alveolar macrophages and human airway epithelial cells to ozone in vitro and measured the cytotoxic effects of ozone, as well as the production of the inflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), and fibronectin, all of which are substantially elevated in the bronchoalveolar lavage fluid of humans exposed to ozone. Cells were grown on rigid, collagen-impregnated filter supports, and the interaction of cells with ozone facilitated by exposing them to the gas with medium below the support but no medium on top of the cells. The results show that, although macrophages are much more sensitive to ozone than epithelial cells, they do not produce increased amounts of IL-6, IL-8, or fibronectin following ozone exposure. In contrast, epithelial cells produce substantially more of all three proteins following ozone exposure, and both IL-6 and fibronectin are secreted vectorially. An immortalized human airway epithelial cell line (BEAS 2B) was used in these experiments since human airway epithelial cells are infrequently available for in vitro studies. Data from this study extend previous findings which suggest that the BEAS cell line is a useful model to study the interaction between airway epithelial cells and environmental toxicants.
Devlin
R B
RB
Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park 27711.
McKinnon
K P
KP
Noah
T
T
Becker
S
S
Koren
H S
HS
D000328:Adult; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010126:Ozone / Q000009:adverse effects / Q000494:pharmacology*
D016207:Cytokines; D005353:Fibronectins; D015850:Interleukin-6; D016209:Interleukin-8; D010126:Ozone