Abstract：
In a Japanese chemical factory, lung diseases such as pneumoconiosis have been reported among workers handling cross-linked water-soluble acrylic acid polymers (CWAAP). Our previous study reported that a single intratracheal administration of CWAAP induces acute inflammation and fibrosis. In this study, we investigated the effects of multiple intratracheal administrations of CWAAP on inflammatory responses and pulmonary fibrosis along with inducible bronchus-associated lymphoid tissues (iBALT) formation, which is involved in allergic inflammation. Male F344 rats (190-200 g) received single or multiple intratracheal administrations of phosphate-buffered saline (PBS) or CWAAP. To assess inflammatory responses and pulmonary fibrosis, immunohistochemical and histological staining was performed. CD68, CD163, CD169, TGF-β, and collagen I positive cells/areas in the lungs of the CWAAP-group rats were significantly increased than those in the PBS group. Furthermore, the number of iBALT structures, CD4 + T cells, along with CD19, PAX5, IL-4, GATA-3, T-bet, and IgE-positive cells in the terminal bronchioles and blood vessels of the lungs were significantly increased in the CWAAP group. Moreover, pulmonary fibrosis, iBALT formation, and levels of specific IgG were significantly increased in rats who received multiple intratracheal administrations of CWAAP compared to those with single intratracheal administration. Multiple intratracheal administrations of CWAAP potentiated the classical fibrotic pathway (M2 macrophage-TGF-β-collagen I) more potently than single intratracheal administration. Furthermore, it was possible that iBALT was formed around terminal bronchioles and blood vessels and the number of immune cells was increased, resulting in enhanced allergic inflammation and pulmonary fibrosis.
摘要：
在一家日本化工厂，在处理交联水溶性丙烯酸聚合物（CWAAP）的工人中，已经报道了诸如尘肺之类的肺部疾病。我们先前的研究报道，气管内单次施用CWAAP可诱导急性炎症和纤维化。在这项研究中,我们研究了多次气管内施用CWAAP对炎症反应和肺纤维化以及可诱导的支气管相关淋巴组织（iBALT）形成的影响，与过敏性炎症有关。雄性F344大鼠（190-200g）接受单次或多次气管内施用磷酸盐缓冲盐水（PBS）或CWAAP。评估炎症反应和肺纤维化，进行免疫组织化学和组织学染色。CD68,CD163,CD169,TGF-β,CWAAP组大鼠肺中胶原I阳性细胞/面积比PBS组显著增加。此外，iBALT结构的数量，CD4+T细胞,以及CD19，PAX5，IL-4，GATA-3，T-bet，在CWAAP组中，终末细支气管和肺血管中的IgE阳性细胞显着增加。此外，肺纤维化，iBALT形成,与单次气管内给药相比，多次气管内给药的大鼠的特异性IgG水平显着增加。CWAAP的多次气管内给药比单次气管内给药更有效地增强了经典的纤维化途径（M2巨噬细胞-TGF-β-胶原蛋白I）。此外，iBALT可能在终末细支气管和血管周围形成，免疫细胞数量增加，导致过敏性炎症和肺纤维化增强。
