title: Role of interferon-gamma in the development of murine bronchus-associated lymphoid tissues induced by silica in vivo.
abstract: Exposure to silica is associated with the development of chronic airflow obstruction as well as pulmonary fibrosis, probably mediated in part by silica-induced small airway disease. To elucidate the mechanism of mucosal immune responses in the small airways, we analyzed the roles of interferon-gamma (IFN-gamma) using mice deficient of this cytokine in silicotic lung. IFN-gamma knockout mice (-/-) and wild-type C57BL/6 mice were treated with either a single fibrogenic dose of silica or an equivalent volume of saline and euthanized 21 days after intratracheal instillation. Total cell counts in bronchoalveolar lavage fluids increased in silica-instilled mice compared to saline-instilled mice, but there were no significant differences between IFN-gamma knockout mice and wild-type mice treated with silica. Morphometric estimation for fibrotic lesions within the lung did not show any differences between these mice. However, bronchus-associated lymphoid tissues (BALT), which are known to be involved in the mucosal immune responses, were significantly larger in the lungs of IFN-gamma knockout mice than in those of wild-type mice treated with silica. In addition, we evaluated the development of BALT in interleukin 4 (IL-4) knockout mice in order to clarify the effect of Th2 cytokine. Morphometric estimation for BALT did not show any differences between IL-4 knockout mice and wild-type mice in silicotic lung. These results suggest that IFN-gamma has an inhibitory effect on the development of BALT and may be involved in small airway disease in silicotic lung.
authors.affiliation: Department of Respiratory Medicine, Graduate School of Medicine, Instutute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Desaki
authors.forename: Isamu
authors.initials: I
authors.lastname: Sugawara
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
mesh_terms: D000818:Animals; D001980:Bronchi / Q000276:immunology*; D005260:Female; D005355:Fibrosis; D006909:Hydroxyproline / Q000032:analysis; D018928:Immunity, Mucosal; D007371:Interferon-gamma / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology; D008221:Lymphoid Tissue / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012822:Silicon Dioxide / Q000633:toxicity*
chemical_list: D015847:Interleukin-4; D012822:Silicon Dioxide; D007371:Interferon-gamma; D006909:Hydroxyproline