Reusens-Billen B, de Clercq L, Barreira V I, Hanotier C J, Remacle C, Hoet J J
Laboratory of Cell Biology, Université Catholique de Louvain, Belgium.
Diabetes Res Clin Pract. 1994 Mar;23(2):85-94. doi: 10.1016/0168-8227(94)90015-9.
Macrophages are present in the initial phase of the autoimmune process involved in the destruction of the endocrine pancreas in IDDM via the secretion of cytokines such as IL-1 beta. Macrophages also secrete lysozyme. Besides its action on the bacterial cell wall, lysozyme has an important physiological and immunological role. Human lysozyme is an in-situ modulator of the inflammatory reactions. We investigate the protective role of human lysozyme in vitro against the cytotoxic effect of IL-1 beta or of IL-1 beta combined with IFN-gamma on isolated rat islets. Precultured newborn rat islets were incubated with human or chicken lysozyme (50.000 U/ml) over 3 days. Human IL-1 beta (100 U/ml) or IL-1 beta (5 U/ml) + INF-gamma (100 U/ml) was added for the last 2 days and tritiated thymidine for the last 24 hrs. In another set of experiments, islets were exposed simultaneously to human lysozyme and IL-1 beta. Only pretreatment with human lysozyme abolished the lowering of the labelling index of the islet cell induced by IL-1 beta or by IL-1 beta and INF-gamma. Pycnotic nuclei were abundant in islets treated with IL-1 alone while they were not when islets were pretreated with human lysozyme. Chicken lysozyme had no protective effect in the same protocol. Human lysozyme was not protective when applied simultaneously with IL-1. Pretreatment of the islets by human lysozyme does not prevent the reduction of the insulin secretion induced by IL-1 beta. Human and chicken lysozyme differ further in their action when tested on fibroblasts proliferation. Only human lysozyme stimulates the latter. In conclusion, only human lysozyme seems to have a protective effect against the cytotoxicity of IL-1 in combination or not with IFN-gamma on islet cells in vitro. Moreover, to be protected, the islets have to be pretreated with lysozyme before the IL-1 application. Our in vitro results imply that natural aspecific immunity and its relation to the secretory function of the macrophage might be crucial for the prevention of the initial assault responsible for the onset of the immune process leading to insulin dependent diabetes.
巨噬细胞存在于自身免疫过程的初始阶段，该过程通过分泌白细胞介素-1β等细胞因子参与胰岛素依赖型糖尿病（IDDM）中内分泌胰腺的破坏。巨噬细胞还分泌溶菌酶。除了对细菌细胞壁的作用外，溶菌酶还具有重要的生理和免疫作用。人溶菌酶是炎症反应的原位调节剂。我们研究了人溶菌酶在体外对白细胞介素-1β或白细胞介素-1β与干扰素-γ联合对分离的大鼠胰岛细胞毒性作用的保护作用。将预培养的新生大鼠胰岛与人或鸡溶菌酶（50000 U/ml）一起孵育3天。在最后2天加入人白细胞介素-1β（100 U/ml）或白细胞介素-1β（5 U/ml）+干扰素-γ（100 U/ml），并在最后24小时加入氚标记的胸腺嘧啶核苷。在另一组实验中，胰岛同时暴露于人溶菌酶和白细胞介素-1β。只有用人溶菌酶预处理才能消除由白细胞介素-1β或白细胞介素-1β与干扰素-γ诱导的胰岛细胞标记指数的降低。单独用白细胞介素-1处理的胰岛中固缩核丰富，而用人溶菌酶预处理的胰岛中则没有。在相同方案中，鸡溶菌酶没有保护作用。与人白细胞介素-1同时应用时，人溶菌酶没有保护作用。用人溶菌酶预处理胰岛并不能阻止白细胞介素-1β诱导的胰岛素分泌减少。在测试对成纤维细胞增殖的作用时，人溶菌酶和鸡溶菌酶的作用进一步不同。只有人溶菌酶能刺激成纤维细胞增殖。总之，只有人溶菌酶似乎对白细胞介素-1单独或与干扰素-γ联合对体外胰岛细胞的细胞毒性具有保护作用。此外，为了得到保护，胰岛必须在应用白细胞介素-1之前用溶菌酶预处理。我们的体外研究结果表明，天然非特异性免疫及其与巨噬细胞分泌功能的关系可能对预防导致胰岛素依赖型糖尿病的免疫过程起始的初始攻击至关重要。
