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1984年3月,我们从Str lukubaensis No1993的发酵液中分离到一种强效免疫抑制剂tacrolimus(曾命名为FK506).自从发现该药物以来,由于其独特的作用方式,以及在动物体上的移植模型和在自身免疫性疾病上取得的显著疗效,引起了人们广泛的兴趣.该药在日本、美国和英国已应用于肝脏、骨髓和肾移植,最近在临床上又被用于抑制组织的排异反应.由于tacrolimus在临床上的重要作用,开发具有相似免疫学模型的新免疫抑制剂就越加显得重要.为了探讨新的筛选这类微生物产物的方法,我们在微生物细胞水平上对tacrolimus的生物学作用进行了广泛的研究,发现tacrolimus对几种敏感真菌的形态表现出特有的作用,如黑曲霉、尖镰孢和白地霉等.令人惊奇的是,真菌产物环孢素A(CsA)的免疫抑制作用相似于tacrolimus,引起了类似的包括变形和菌丝端分支等形态学上的变化,而雷帕霉素(rapamycin)则被失活.雷帕霉素是一种大环内酯类免疫抑制剂,与tacrolimus有相似的化学结构,但其作用方式不同.此外,其它抗真菌抗生素如放线菌酮和两性霉素B缺乏免疫抑制活性,由于tacrolimus类似物,包括 FR900520 和FR900512,也同样有引起独特真菌形态变化的特性.所以推断tacrolimus和CsA引起的形态学上的反应,可能与它们共有的免疫抑制机制有密切的关系,包
In March 1984, we isolated a potent immunosuppressant, tacrolimus (formerly named FK506) from the fermentation broth of Strukubaensis No 1993. Because of its unique mode of action and its discovery in animals, Transplantation models and the notable efficacy achieved in autoimmune diseases have drawn widespread interest and have been used in liver, bone marrow and kidney transplants in Japan, the United States, and the United Kingdom, and have recently been used clinically to inhibit tissue Rejection due to the clinically important role of tacrolimus, the development of new immunosuppressive agents with similar immunological models becomes even more important.In order to explore new methods of screening for such microbial products, we investigated the level of tacrolimus Has been extensively studied and found that tacrolimus exhibits specific effects on the morphology of several sensitive fungi such as Aspergillus niger, Fusarium oxysporum and Geotrichum candidum etc. Surprisingly, the fungal product Cyclosporin A ( CsA) is immunosuppressive similar to tacrolimus, causing similar morphological changes including deformation and mycelium-terminal branching, whereas rapamycin is Inactivation rapamycin is a macrolide immunosuppressant with tacrolimus has a similar chemical structure, but its mode of action is different.In addition, other antifungal antibiotics such as cycloheximide and amphotericin B deficiency Immunosuppressive activity is also characterized by unique morphological changes caused by tacrolimus analogues, including FR900520 and FR900512, so it is concluded that the morphological responses induced by tacrolimus and CsA may be closely related to their common immunosuppressive mechanisms ,package