Immunomodulating effects of ozone on macrophage functions important for tumor surveillance and host defense.
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 phi) responses as a possible mechanism by which O3 may influence carcinogenesis, we examined the effects of repeated in vivo O3 exposure on pulmonary M phi 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 phi viability and increased the number of neutrophils collected immediately after exposure. Effects of O3 on M phi movement were as follows: random migration was depressed immediately after the final exposure and chemotactic migration increased after 24 h. M phi-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 LM cells (a clone of L-929 mouse fibroblasts), was unaffected by exposure to O3. Zymosan-stimulated production of superoxide anion radical (.O2-) was depressed at t0 and increased at t24; however, no significant effects on H2O2 production by resting or zymosan-stimulated M phi were observed at either time interval. Inhaled toxicants such as O3, which can compromise M phi 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.
Zelikoff
J T
JT
Institute of Environmental Medicine, New York University Medical Center, NY 10016.
Kraemer
G L
GL
Vogel
M C
MC
Schlesinger
R B
RB
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D002464:Cell Migration Inhibition; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D008297:Male; D010126:Ozone / Q000633:toxicity*; D011817:Rabbits; D013047:Specific Pathogen-Free Organisms; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D010126:Ozone; D006861:Hydrogen Peroxide