CD4+ T lymphocyte modulation of ozone-induced murine pulmonary inflammation.
Inhalation of elevated levels of ozone produces a potent inflammatory response in the lung. The magnitude of this response to ozone exposure in mice is inbred strain dependent with the susceptible phenotype being exemplified by the C57BL/6J (B6) strain and the resistant phenotype by the C3H/HeJ (C3) strain. To examine the role of T lymphocytes in the regulation of ozone-induced pulmonary inflammation, mice were pretreated by an intraperitoneal injection of anti-Thy1.2 monoclonal antibody (mAb), anti-CD4+ mAb, or isotype-matched control antibodies (0.5 mg each) and subsequently exposed for 72 h to either filtered air or ozone (0.3 ppm). Immediately after ozone exposure, the cellular profile in the bronchoalveolar lavage fluids (BALF) was assessed. In isotype-treated controls of both strains of mice, ozone exposure induced significant increases in the numbers of macrophages, neutrophils, lymphocytes, and epithelial cells recovered in the BALF; however, the magnitude of each cell type recovered was significantly greater in B6 mice as compared with C3 mice. Both anti-Thy1.2 and anti-CD4+ monoclonal antibody treatments decreased the number of each cell type recovered in the B6 mice and increased the number of cells in the C3 mice. To determine if the CD4+ T-cell-derived cytokine interleukin (IL)-4 was involved in the differential effect of T-cell depletion on the ozone-induced inflammatory responses of C3 and B6 mice, mice were pretreated with either 400 ng of recombinant mouse IL-4 or vehicle, or 5.0 mg anti-IL-4 receptor monoclonal antibody or an isotype-matched antibody before either air or ozone exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Chen
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Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Gavett
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Wills-Karp
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D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015847:Interleukin-4 / Q000502:physiology; D008168:Lung / Q000187:drug effects*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000037:antagonists & inhibitors
D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D010126:Ozone