Minami Junko, Eishi Yoshinobu, Ishige Yuki, Kobayashi Intetsu, Ishige Ikuo, Kobayashi Daisuke, Ando Noboru, Uchida Keisuke, Ikeda Satoshi, Sorimachi Noriko, Karasuyama Hajime, Takemura Tamiko, Takizawa Touichiro, Koike Morio
Department of Human Pathology, Tokyo Medical and Dental University, Japan.
J Med Dent Sci. 2003 Dec;50(4):265-74.
Etiology of sarcoidosis remains unknown. A trigger factor from Propionibacterium acnes causes a cellular immune response in some sarcoid patients but not in nonsarcoid subjects. We examined whether experimentally induced hypersensitivity to the trigger factor gives rise to granulomas. Female C57BL/6 mice primed intravenously with P. acnes or not were sensitized with recombinant-protein RP35, a fragment of P. acnes trigger factor, and complete Freund's adjuvant. In controls, RP35 was replaced with P. acnes or one of two control proteins. In primed and unprimed mice, pulmonary granulomas were found in some of the mice sensitized with RP35 or P. acnes but in no control-protein-sensitized mice. Detection of pulmonary granulomas (25-57%) did not differ significantly between mice sensitized with RP35 or P. acnes, primed or not. No difference in popliteal lymph-node-cell reactivity and serum antibodies to these two antigens was found between mice with and without pulmonary granulomas. P. acnes was cultured from the lungs of 8 (33%) of 24 untreated mice. The recombinant trigger-factor protein of P. acnes caused pulmonary granulomas in primed and unprimed mice sensitized with the protein and adjuvant. Sarcoid granulomas may form during hypersensitivity to antigens of P. acnes indigenous to the affected organ.
结节病的病因尚不清楚。痤疮丙酸杆菌的一种触发因子在一些结节病患者中引发细胞免疫反应,但在非结节病患者中则不会。我们研究了实验性诱导的对该触发因子的超敏反应是否会导致肉芽肿形成。对雌性C57BL/6小鼠静脉注射痤疮丙酸杆菌进行预处理或不进行预处理,然后用痤疮丙酸杆菌触发因子的片段重组蛋白RP35和完全弗氏佐剂进行致敏。在对照组中,用痤疮丙酸杆菌或两种对照蛋白之一替代RP35。在预处理和未预处理的小鼠中,在用RP35或痤疮丙酸杆菌致敏的一些小鼠中发现了肺部肉芽肿,但在对照蛋白致敏的小鼠中未发现。在用RP35或痤疮丙酸杆菌致敏的小鼠中,无论是否进行预处理,肺部肉芽肿的检出率(25%-57%)无显著差异。有和没有肺部肉芽肿的小鼠之间,腘窝淋巴结细胞反应性以及针对这两种抗原的血清抗体均无差异。在24只未经治疗的小鼠中,有8只(33%)的肺部培养出痤疮丙酸杆菌。痤疮丙酸杆菌的重组触发因子蛋白在用该蛋白和佐剂致敏的预处理和未预处理小鼠中均导致了肺部肉芽肿。结节病肉芽肿可能在对患病器官中存在的痤疮丙酸杆菌抗原的超敏反应过程中形成。