Badger A M, King A G, Talmadge J E, Schwartz D A, Picker D H, Mirabelli C K, Hanna N
Department of Immunology, Smith Kline Beecham Pharmaceuticals, King of Prussia, PA 19406.
J Autoimmun. 1990 Aug;3(4):485-500. doi: 10.1016/s0896-8411(05)80015-0.
SK&F 105685 (N,N-Dimethyl-8,8-dipropyl-2-azaspiro[4,5]decane-2- propanamine dihydrochloride) is a novel azaspirane which has therapeutic activity in rat models of autoimmune disease. In this study, we have demonstrated that SK&F 105685 is a potent inducer of non-specific suppressor cells (SC). Oral administration of 15-30 mg/kg/day results in the generation of SC in the spleen, lymph nodes and bone marrow, but not the thymus of Lewis rats. Splenic SC suppress Con-A-induced proliferation in co-culture assays at effector-responder ratios of 1:1 to 1:64. SC are radiation resistant (2000 R), non-T, non-B cells, partially adherent to plastic surfaces and are enriched in a 1.07 g/ml fraction of a Percoll density gradient. Their activity is increased, rather than ablated, by indomethacin. No definitive changes in Ig+, OX-19+, OX-8+, W3/25+ or asialo GM1+ cells could be detected in the spleens of treated rats compared to control untreated animals. Elevated levels of both radiation-sensitive and radiation-resistant suppressor cells were found in the bone marrow of treated rats in addition to the radiosensitive SC normally present in this tissue.
SK&F 105685（N，N-二甲基-8，8-二丙基-2-氮杂螺[4,5]癸烷-2-丙胺二盐酸盐）是一种新型氮杂螺环化合物，在自身免疫性疾病大鼠模型中具有治疗活性。在本研究中，我们证明SK&F 105685是一种强效的非特异性抑制细胞（SC）诱导剂。每天口服15 - 30毫克/千克可导致Lewis大鼠的脾脏、淋巴结和骨髓中产生SC，但胸腺中不会产生。在共培养试验中，脾脏SC在效应细胞与反应细胞比例为1:1至1:64时可抑制刀豆蛋白A诱导的增殖。SC具有辐射抗性（2000拉德），是非T、非B细胞，部分粘附于塑料表面，并且在Percoll密度梯度的1.07克/毫升组分中富集。吲哚美辛可增强而非消除它们的活性。与未处理的对照动物相比，在处理过的大鼠脾脏中未检测到Ig +、OX - 19 +、OX - 8 +、W3/25 +或去唾液酸GM1 +细胞有明确变化。除了该组织中正常存在的辐射敏感SC外，在处理过的大鼠骨髓中还发现了辐射敏感和辐射抗性抑制细胞水平升高。
