Expansion of interferon-gamma-producing lung lymphocytes in mouse silicosis.
Silicosis is characterized by mononuclear cell inflammation with macrophage activation, accumulation of lymphocytes, and fibrosis. Interferon-gamma (IFN-gamma) is a lymphocyte cytokine with broad effects, particularly macrophage activation. Mice exposed to an aerosol of cristobalite silica (70 mg/m3, 12 d, 5 h/d) developed diffuse pulmonary pathologic changes with macrophage, lymphocyte, and neutrophil recruitment, and increased lung collagen. IFN-gamma messenger RNA (mRNA) was more abundant by semiquantitative reverse transcription-polymerase chain reaction in the lungs of silica-exposed mice than in control animals. IFN-gamma mRNA transcripts were detected by in situ hybridization with digoxigenin-labeled complementary DNA probes in normal mouse lung tissue within bronchial-associated lymphoid tissues (BALT). In silica- exposed mice, mononuclear cells with IFN-gamma mRNA were more numerous in the silicotic lesions and enlarged BALT structures. Lung-cell suspensions were prepared by enzyme digestion, stained with fluorescent-labeled antibodies against intracellular cytokines, and enumerated by flow cytometry. The percentage of cells producing IFN-gamma was increased in silicotic mice (19% versus 11%). Interleukin (IL)-4 mRNA transcripts were less abundant in the lung tissue from silica-exposed mice than in control mice. Cells staining for IL-4 mRNA were found rarely in either the air-sham or the silica-exposed mouse lungs, and almost all appeared to be within BALT structures. Approximately 3% of cells stained for IL-4 in the digested lungs from both groups. Similar cytokine patterns were observed in mediastinal lymph node/thymus and spleen tissues. The augmented IFN-gamma response, with IL-4 unchanged or decreased, in the lung lesions and lymphoid tissue of mice with silicosis suggests a Th-1-like lymphocyte-mediated immune-inflammatory response.
Davis
G S
GS
Departments of Medicine & Civil and Mechanical Engineering, University of Vermont, Burlington, Vermont, USA. gdavis1@zoo.uvm.edu
Pfeiffer
L M
LM
Hemenway
D R
DR
D000336:Aerosols; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D017931:DNA Primers; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D012822:Silicon Dioxide / Q000008:administration & dosage; D012829:Silicosis / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D014158:Transcription, Genetic
D000336:Aerosols; D017931:DNA Primers; D012333:RNA, Messenger; D015847:Interleukin-4; D012822:Silicon Dioxide; D007371:Interferon-gamma