Goya Sho, Matsuoka Hiroto, Mori Masahide, Morishita Hiroshi, Kida Hiroshi, Kobashi Yoichiro, Kato Terufumi, Taguchi Yoshio, Osaki Tadashi, Tachibana Isao, Nishimoto Norihiro, Yoshizaki Kazuyuki, Kawase Ichiro, Hayashi Seiji
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
J Pathol. 2003 May;200(1):82-7. doi: 10.1002/path.1321.
A variety of pathological changes are seen in lymphoproliferative disorders of the lung but the histogenesis of these abnormalities is not yet fully understood. We previously showed that adenovirus vector-mediated transient expression of both the human interleukin-6 (IL-6) and IL-6 receptor (IL-6R) genes, but not the IL-6 gene alone, in the rat lung induced lymphocytic alveolitis. In the present study, we explored the lung pathology of human IL-6 and IL-6R double transgenic mice to elucidate the effects of prolonged IL-6 signalling on the lung. The transgenic animals developed mononuclear cell accumulation in peribronchovascular regions, but little infiltration into alveolar spaces. Immunohistochemical analysis revealed that the cellular accumulations contained not only mixtures of inflammatory cells but also lymphoid tissue-like structures. As the expression of CXCL13/BLC, the indispensable chemokine for lymphoid organogenesis, was recognized in the B cell follicles of the pulmonary lesions, we speculate that this chemokine plays an inductive role in the development of the lymphoid tissue-like structures. These structures were distinguished from bronchus-associated lymphoid tissues (BALTs) by their location and by the lack of lymphoepithelium, which is a characteristic of BALT. These findings imply that IL-6 signalling may play a role in the pathogenesis of lymphoproliferative disorders of the lung.
在肺部淋巴增殖性疾病中可见多种病理变化，但这些异常的组织发生尚未完全明确。我们之前表明，腺病毒载体介导的人白细胞介素6（IL-6）和IL-6受体（IL-6R）基因在大鼠肺中瞬时共表达（而非单独表达IL-6基因）可诱导淋巴细胞性肺泡炎。在本研究中，我们探究了人IL-6和IL-6R双转基因小鼠的肺部病理情况，以阐明IL-6信号长期存在对肺的影响。转基因动物在支气管血管周围区域出现单核细胞聚集，但很少浸润到肺泡腔。免疫组织化学分析显示，细胞聚集不仅包含炎性细胞混合物，还包含淋巴样组织结构。由于在肺部病变的B细胞滤泡中发现了淋巴器官发生所必需的趋化因子CXCL13/BLC的表达，我们推测这种趋化因子在淋巴样组织结构的形成中起诱导作用。这些结构在位置上以及缺乏作为支气管相关淋巴组织（BALT）特征的淋巴上皮方面与BALT不同。这些发现表明，IL-6信号可能在肺部淋巴增殖性疾病的发病机制中起作用。
