Immunomodulating effects of ozone on macrophage functions important for tumor surveillance and host defense

Abstract

Ozone (O₃) is a toxic gaseous pollutant that has been implicated in laboratory studies as a potential lung carcinogen or cocarcinogen in mice. To begin to assess the role of altered macrophage (M⊘) responses as a possible mechanism by which O₃ may influence carcinogenesis, we examined the effects of repeated in vivo O₃ exposure on pulmonary M⊘ functional and biochemical activities deemed important in tumor surveillance, and host defense in general. Rabbits were exposed by inhalation to 1 ppm O₃ for 3 d (2 h/d) and the lungs were lavaged immediately (t₀) and 24 h (t₂₄) after exposure. Results demonstrate that O₃ reduced M⊘ viability and increased the number of neutrophils collected immediately after exposure. Effects of O₃ on M⊘ movement were as follows: random migration was depressed immediately after the final exposure and chemotactic migration increased after 24 h. M⊘‐mediated cytotoxicity toward xenogeneic tumor cells in vitro was significantly depressed, compared to control, immediately and 24 h after O₃ exposure. Release of cytotoxic factors deemed important for mediating tumor cell destruction was also assessed. Spontaneous and stimulated production of tumor necrosis factor, as measured by cytotoxicity toward L‐M cells (a clone of L‐929 mouse fibrobtasts), was unaffected by exposure to O₃. Zymosan‐stimulated production of superoxide anion radical (·O⁻ ₂) was depressed at t₀ and increased at t₂₄; however, no significant effects on H₂O₂ production by resting or zymosan‐stimulated M⊘ were observed at either time interval. Inhaled toxicants such as O₃, which can compromise M⊘ functions important in tumor surveillance, could potentially alter host susceptibility to pulmonary cancer. Results of this study have important implications for human health, and demonstrate the need for further studies examining the carcinogenic/cocarcinogenic potential of O₃.