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

感染巴西拟青霉线虫可引起组织嗜酸性粒细胞增多、肥大细胞数量增加，幼虫通过该器官迁徙后可在大鼠肺内形成肉芽肿。该肺部病变类似于Loeffler综合征，即派综合征之一。为了解肥大细胞在肺部病变发展中的作用，我们观察了先天性肥大细胞缺陷Ws/Ws大鼠体内线虫诱导的组织嗜酸性粒细胞增多和肉芽肿形成。Ws/Ws组和对照组+/+组大鼠肺内蠕虫数量和迁移时间无明显差异。初次感染后1-7天和攻击感染后1-7天，嗜酸性粒细胞增多。Ws/Ws大鼠肺组织和支气管肺泡灌洗液中的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天出现。肉芽肿由上皮样细胞、多核巨细胞、嗜酸性粒细胞和肥大细胞组成。攻击感染后第28天，肉芽肿生长较快，攻击感染后3d达到高峰，且肉芽肿大小明显大于初次感染。与+/+大鼠相比，Ws/Ws大鼠的肉芽肿形成明显受到抑制，尤其是攻击感染后的肉芽肿形成。在+/+大鼠中，初次感染后肥大细胞数量显著增加。攻击感染后1~3天，肥大细胞数量短暂减少，提示肥大细胞被激活和破坏。观察到肺组织提取液中组胺和大鼠肥大细胞蛋白酶II的水平在这一时期下降，这支持了这一点。这些结果表明，肥大细胞在肺肉芽肿和组织嗜酸性粒细胞的发生发展中起重要作用。

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.