Okumura Yoshiyuki, Ogawa Kenji, Uchiya Kei-Ichi, Komori Yumiko, Nonogaki Tsunemasa, Nikai Toshiaki
Department of Validation, Matsuurayakugyo Co., Ltd., Nagoya, Aichi, Japan.
Nihon Ishinkin Gakkai Zasshi. 2008;49(2):87-93. doi: 10.3314/jjmm.49.87.
The biological properties of elastase inhibitor from Aspergillus flavus (AFLEI) were investigated. AFLEI was produced at the highest rate when casamino acid was used as the nitrogen source. When a mixture of AFLEI (approx. molecular weight, 7,500) and elastase from A. flavus (approx. molecular weight, 40,000) was detected using anti-AFLEI antibody, molecular weight of the detected mixture was approximately 48,000, indicating that AFLEI and elastase bound at a proportion of 1 : 1. When immunocompromised mice administrered of immunosuppressive (cyclophosphamide) were infected by inhalation of A. flavus and administered amphotericin B (AMB) alone or in combination with AFLEI, survival rate tended to be higher with combination treatment than with AMB alone. Moreover, although extensive bleeding was seen in pathology sections taken from rat lung resected 24 hr after purified elastase was administered to the lung via the bronchus, this bleeding was inhibited by AFLEI. These findings indicate that for the treatment of aspergillosis, combination of an existing antifungal agent with AFLEI can be expected to provide greater therapeutic benefits than administration of an antifungal agent alone.
对来自黄曲霉的弹性蛋白酶抑制剂(AFLEI)的生物学特性进行了研究。当使用酪蛋白氨基酸作为氮源时,AFLEI的产量最高。使用抗AFLEI抗体检测AFLEI(分子量约为7500)和来自黄曲霉的弹性蛋白酶(分子量约为40000)的混合物时,检测到的混合物的分子量约为48000,这表明AFLEI和弹性蛋白酶以1:1的比例结合。当通过吸入感染黄曲霉并单独或与AFLEI联合给予两性霉素B(AMB)时,免疫受损小鼠(接受免疫抑制剂环磷酰胺治疗)联合治疗的生存率往往高于单独使用AMB的情况。此外,尽管在经支气管向大鼠肺部注射纯化弹性蛋白酶24小时后切除的大鼠肺组织病理切片中观察到广泛出血,但AFLEI可抑制这种出血。这些发现表明,对于曲霉病的治疗,将现有的抗真菌药物与AFLEI联合使用有望比单独使用抗真菌药物提供更大的治疗益处。