Pulmonary and hepatic effects of inhaled ozone in rats

Journal Article · Thu Dec 01 04:00:00 EST 1994 · Environmental Health Perspectives

DOI:https://doi.org/10.1289/ehp.94102s1061· OSTI ID:494239

Laskin, D L; Pendino, K J; Punjabi, C J ^[1]

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1. Rutgers Univ., Piscataway, NJ (United States)

Nitric oxide is a highly reactive molecule that has been implicated in host defense and in tissue injury. In the present studies we analyzed the effects of brief exposure of rats to inhaled ozone on production of this mediator by lung macrophages and type II epithelial cells. We found that ozone exposure (1-2 ppm, 3 hr) induced a marked increase in spontaneous nitric oxide production by alveolar (AM) and interstitial macrophages, as well as type II cells. These effects were apparently due to increased expression of inducible nitric oxide synthase protein and mRNA, which was evident in vitro in isolated cells and in situ in histologic sections. Macrophages and epithelial cells from ozone-treated rats were also sensitized to product increased amounts of nitric oxide in response to inflammatory cytokines such as interferon-{gamma}, a response that was also mediated by inducible nitric oxide synthase. Unexpectedly, we also discovered that brief inhalation of ozone caused dramatic effects on the liver, including increased production of nitric oxide by hepatocytes and enhanced protein synthesis. These data suggest that this inhaled irritant induces an acute phase response. Additional studies indicated that AM from ozone-treated rats produced significantly more tumor necrosis factor-{alpha} and interleukin-1 than did cells from control animals. Elevated levels of tumor necrosis factor-{alpha} were also noted immunohistochemically in both lung and liver tissue. These results indicate that the extrapulmonary effects of ozone may be mediated by inflammatory cytokines released by activated lung macrophages. Taken together our data demonstrate that acute exposure of rats to ozone activated lung macrophages and type II epithelial cells to release cytotoxic and proinflammatory mediators that we speculate contribute to the pathophysiologic effects of this oxidant on the lung and the liver. 31 refs., 2 tabs.

• Sponsoring Organization: USDOE
• OSTI ID: 494239
• Report Number(s): CONF-9308288--; CNN: Grant ES04738; Grant ES05022
• Journal Information: Environmental Health Perspectives, Journal Name: Environmental Health Perspectives Journal Issue: Suppl.10 Vol. 102; ISSN 0091-6765; ISSN EVHPAZ
• Country of Publication: United States
• Language: English

Related Subjects

54 ENVIRONMENTAL SCIENCES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
ACUTE EXPOSURE
AIR POLLUTION
BIOLOGICAL EFFECTS
CLIMATIC CHANGE
INHALATION
INTERFERON
MACROPHAGES
NECROSIS
NITRIC OXIDE
OZONE
RATS