STUDIES ON THE PATHOGENESIS OF PIE SYNDROME INDUCED BY NEMATODE INFECTION,WITH SPECIAL REFERENCE TO THE ROLE OF MAST CELLS.

巴西尼波圆线虫感染后，经肺迁移的大鼠肺组织嗜酸性细胞增多，肥大细胞数量增加，并形成肉芽肿。肺病变类似于Loeffler综合征，即PIE综合征之一。为了了解肥大细胞在肺病变发展中的作用，我们研究了线虫诱导的组织嗜酸性粒细胞增多和肉芽肿形成的先天性肥大细胞缺陷Ws/Ws大鼠。肺内蠕虫数量和通过肺迁移的时间过程在w / w和对照+/+大鼠之间没有差异。嗜酸性粒细胞在初次感染后1-7天以及攻毒感染后增加。Ws/Ws大鼠肺组织和支气管肺泡灌洗液中嗜酸性粒细胞数量明显少于+/+大鼠。在+/+大鼠中，肉芽肿在初次感染后7天发生。肉芽肿由上皮样细胞、多核巨细胞、嗜酸性细胞和肥大细胞组成。攻毒后第28天肉芽肿发展速度加快，在攻毒后第3天达到高峰，肉芽肿大小显著大于初发感染时。与+/+大鼠相比，Ws/Ws大鼠肉芽肿的形成，特别是攻毒感染后的肉芽肿形成明显受到抑制。在+/+大鼠中，原发感染后肥大细胞数量明显增加。攻毒后1-3天后，肥大细胞数量短暂减少，提示肥大细胞被激活并可见。观察到肺组织提取物中组胺和大鼠肥大细胞蛋白酶II的水平在这一时期下降，这一点得到了支持。这些结果表明肥大细胞在肺肉芽肿和组织嗜酸性粒细胞增多的发展中起重要作用。

Infection with the nematode Nippostrongylus brasiliensis induces tissue eosinophilia, increases of the number of mast cells, and development of granulomas in rat lung after the migration of larvae through this organ. This lung lesion resembled Loeffler's syndrome, that is one of PIE syndrome. To know the role of mast cells in the development of lung lesion, we investigated the nematode-induced tissue eosinophilia and granuloma formation in congenitally mast cell-deficient Ws/Ws rats. Numbers of the worms in the lung and the time course of migration through the lung did not differ between Ws/Ws and control +/+ rats. Eosinophils increased 1-7 days after primary as well as after the challenge infection. The numbers of eosinophils in the lung tissue and in bronchoalveolar lavage fluid were significantly smaller in Ws/Ws rats than in +/+ rats. In +/+ rats, granulomas developed 7 days after the primary infection. The granulomas consists of epithelioid cells, multinucleate giant cells, eosinophils and mast cells. After challenge infection on day 28, granulomas developed more quickly, peaked 3 days after the challenge infection, and the granuloma size was significantly larger than that in primary infection. Compared to +/+ rats, the granuloma formation, especially that after the challenge infection, was significantly suppressed in Ws/Ws rats. In +/+ rats, the number of mast cells markedly increased after the primary infection. After the challenge infection, the numbers decreased transiently 1-3 days later, suggesting that mast cells were activated and invisualized. This was supported by the observations that the levels of histamine and rat mast cell protease II in the lung tissue extract were decreased at this period. These results indicate that mast cells play an important role for the development of granuloma and tissue eosinophilia in the lung.