Kohnert K D, Ziegler B, Hehmke B, Fält K, Odselius R, Ziegler M
Department of Central Laboratory, Central Institute of Diabetes, Karlsburg, German Democratic Republic.
Int J Pancreatol. 1990 Jan;6(1):33-48. doi: 10.1007/BF02924342.
The possible relationship between destruction of pancreatic beta cells and islet cell surface antibodies (ICSA) was examined in a rat model using complete Freund's adjuvant (CFA), a lymphocyte activator, in combination with the beta cell toxin, streptozotocin (STZ). In addition to this treatment, the rat insulinoma cell line, RIN5AH, as a readily accessible source of insulin-producing cells, was utilized to potentiate the production of ICSA. Intraperitoneal injections of CFA to male Lewis rats, followed 24 h later by a single nondiabetogenic dose of STZ, produced a 47% (p less than 0.01) reduction in pancreatic insulin content associated with degranulation and necrosis of insulin-immunoreactive cells. Eight weeks after treatment, ICSA were detectable that mediated the complement-dependent lysis of neonatal rat islet cells. Injections of RIN5AH cells, following treatment with CFA/STZ, did neither increase the severity of histopathological changes in the exocrine pancreas nor the extent of beta cell necrosis, but gave rise to higher levels of cytotoxic ICSA. Immunization with RIN cells alone, although increasing ICSA levels above those of the other experimental groups, produced no major histopathological changes. These results indicate that ICSA are the consequence of beta cell damage, and they are not capable of promoting or initiating beta cell necrosis in this model.
在大鼠模型中，使用淋巴细胞激活剂完全弗氏佐剂（CFA）联合β细胞毒素链脲佐菌素（STZ），研究了胰腺β细胞破坏与胰岛细胞表面抗体（ICSA）之间可能存在的关系。除了这种处理方式外，大鼠胰岛素瘤细胞系RIN5AH作为易于获取的胰岛素产生细胞来源，被用于增强ICSA的产生。给雄性Lewis大鼠腹腔注射CFA，24小时后再注射单次非致糖尿病剂量的STZ，导致胰腺胰岛素含量降低47%（p<0.01），伴有胰岛素免疫反应性细胞的脱颗粒和坏死。治疗8周后，可检测到介导新生大鼠胰岛细胞补体依赖性溶解的ICSA。在CFA/STZ处理后注射RIN5AH细胞，既未增加外分泌胰腺组织病理学变化的严重程度，也未增加β细胞坏死的程度，但产生了更高水平的细胞毒性ICSA。单独用RIN细胞免疫，虽然使ICSA水平高于其他实验组，但未产生主要的组织病理学变化。这些结果表明，ICSA是β细胞损伤的结果，在该模型中它们不能促进或引发β细胞坏死。
