Effects of cyclosporine A on ozone-induced pulmonary lesion formation: pharmacologic elimination of the T-lymphocyte regulatory response.
To assess the involvement of T-lymphocytes in ozone-induced lung damage, CD-1 mice were exposed to air or 0.7 ppm ozone (1.37 mg O3/m3 air) in the presence and absence of the immunosuppressive drug cyclosporine A (CSA). Mice were thus divided into four treatment groups for both the 4 and 14 day exposure times: 1) AIR + VEH, 2) AIR + CSA, 3) O3 + VEH, and 4) O3 + CSA. Thy-1.2 positive cells (T-lymphocytes) per pulmonary lesion were determined and quantitative histomorphometric analysis of lesion volume was performed. By Day 14, the number of T-lymphocytes per lesion in O3 + VEH (vehicle) animals had increased to approximately 3.5 times that seen at Day 4. At 4 and 14 days of O3 + CSA treatment, the number of T cells per lesion was half that seen in O3 + VEH mice. At Day 4, lesion size and appearance were comparable in O3 + VEH and O3 + CSA animals, while at Day 14, O3 + CSA treatment resulted in larger and more cellular lesions that contained a greater proportion of polymorphonuclear cells, and the lesions extended further into the lung periphery. Inflammatory cells were observed in areas of epithelial cell proliferation and in alveolar spaces distal to the small airway terminus. After 14 days, lesion volume was approximately twice as great following O3 + CSA administration than with O3 treatment alone. These results are consistent with effects seen in another model of immunosuppression, the nude mouse, and they implicate a regulatory role for T-lymphocytes in the response to ozone.
Bleavins
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Automotive Safety and Health Department, General Motors Research and Development Center, Warren, Michigan 48090-9055.
Sargent
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NE
Dziedzic
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D
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008198:Lymph Nodes / Q000187:drug effects; D051379:Mice; D010126:Ozone / Q000633:toxicity*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
D010126:Ozone; D016572:Cyclosporine