Role of interferon-gamma in the development of murine bronchus-associated lymphoid tissues induced by silica in vivo.
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.
Desaki
Masashi
M
Department of Respiratory Medicine, Graduate School of Medicine, Instutute of Medical Science, University of Tokyo, Tokyo, Japan.
Sugawara
Isamu
I
Iwakura
Yoichiro
Y
Yamamoto
Kazuhiko
K
Takizawa
Hajime
H
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*
D015847:Interleukin-4; D012822:Silicon Dioxide; D007371:Interferon-gamma; D006909:Hydroxyproline