Yokohira Masanao, Yamakawa Keiko, Nakano Yuko, Numano Takamasa, Furukawa Fumio, Kishi Sosuke, Ninomiya Fumiko, Kanie Shohei, Hitotsumachi Hiroko, Saoo Kousuke, Imaida Katsumi
Onco-Pathology, Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya, Aichi 491-0113, Japan.
J Toxicol Pathol. 2014 Oct;27(3-4):175-82. doi: 10.1293/tox.2014-0020. Epub 2014 Jun 9.
Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were examined and compared immunohistochemically. Formalin fixed paraffin embedded (FFPE) lung samples featuring inflammation were obtained with a rat quartz instillation model, and neoplastic lesions, hyperplasias and adenomas, were obtained with the rat DHPN-induced lung carcinogenesis model. In the rat quartz instillation model, male 10-week old F344 rats were exposed by intratracheal instillation (IT) to quartz at a dose of 2 mg/rat suspended in saline (0.2 ml) on day 0, and sacrificed on day 28. Lung tumorigenesis in F344 male rats was initiated by DHPN in drinking water for 2 weeks, and the animals were then sacrificed in week 30. Lung proliferative lesions, hyperplasias and adenomas, were observed with DHPN, and inflammation was observed with quartz. The expressions of SP-A, SP-B, SP-C and SP-D were examined immunohistochemically. SP-B and SP-C showed strong expression in lung hyperplasias and adenomas, while SP-A and SP-D were observed in mucus or exudates in inflammatory alveoli. These results suggest the possibility that SP-B and SP-C are related to lung tumorigenesis.
表面活性蛋白(SPs)最初被称为人肺表面活性剂,对呼吸结构和功能至关重要。它有4种亚型,即SP-A、SP-B、SP-C和SP-D,其中SP-A和SP-D具有免疫功能,而SP-B和SP-C具有降低生物界面表面张力的物理化学特性。在本实验中,采用免疫组织化学方法检测并比较了N-双(2-羟丙基)亚硝胺(DHPN)诱导的肺肿瘤病变以及石英注入所致炎症病变中SP-A、SP-B、SP-C和SP-D的表达。利用大鼠石英注入模型获取了具有炎症的福尔马林固定石蜡包埋(FFPE)肺样本,并利用大鼠DHPN诱导的肺癌发生模型获取了肿瘤病变、增生和腺瘤样本。在大鼠石英注入模型中,于第0天经气管内注入(IT)将剂量为2mg/只的石英悬浮于生理盐水(0.2ml)中,对10周龄雄性F344大鼠进行暴露,并于第28天处死。通过在饮用水中加入DHPN启动F344雄性大鼠的肺肿瘤发生,持续2周,然后在第30周处死动物。观察到DHPN导致肺增殖性病变、增生和腺瘤,石英导致炎症。采用免疫组织化学方法检测SP-A、SP-B、SP-C和SP-D的表达。SP-B和SP-C在肺增生和腺瘤中呈强表达,而SP-A和SP-D在炎性肺泡的黏液或渗出物中可见。这些结果提示SP-B和SP-C可能与肺肿瘤发生有关。