Gupta A A, Leal-Berumen I, Croitoru K, Marshall J S
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
J Immunol. 1996 Sep 1;157(5):2123-8.
Mast cells have been reported to secrete a wide range of immunoregulatory cytokines following IgE-mediated activation and to play an important role in allergic inflammation. We have previously demonstrated that mast cells can also produce certain cytokines following activation with bacterial LPS or prostanoids without preformed mediator release. IL-12 is a potent inducer of IFN-gamma production by T cells and NK cells, and is thought to play a critical role in determining the nature of the local immune response to infection. We here report that highly purified peritoneal mast cells from Brown Norway rats will produce IFN-gamma in response to IL-12 without significant histamine release. IFN-gamma protein was detected by ELISA in supernatants of mast cells cultured with 2 U/ml recombinant mouse IL-12 for between 6 and 24 h. The production of IFN-gamma was dependent on the dose of IL-12 and was significantly inhibited by concurrent treatment with IL-10 or PGE2. Supernatants from IL-12-stimulated mast cells induced MHC class II expression on the mouse epithelial cell line, MODE-K, by an IFN-gamma-dependent mechanism. Peritoneal mast cells cultured following activation with anti-IgE or LPS, under conditions that will induce the production of IL-6, demonstrated no detectable protein production of IFN-gamma. We conclude that mast cells are capable of contributing to the IFN-gamma response to IL-12, but substantial mast cell IFN-gamma production does not occur as a result of IgE-mediated activation. These observations have important implications for the role of the mast cell in local immune regulation.
据报道，肥大细胞在IgE介导的激活后可分泌多种免疫调节细胞因子，并在过敏性炎症中发挥重要作用。我们之前已经证明，肥大细胞在用细菌脂多糖（LPS）或前列腺素激活后，也能产生某些细胞因子，且不会预先释放介质。白细胞介素12（IL-12）是T细胞和自然杀伤细胞（NK细胞）产生γ干扰素（IFN-γ）的有效诱导剂，被认为在决定局部感染免疫反应的性质方面起着关键作用。我们在此报告，来自棕色挪威大鼠的高度纯化的腹膜肥大细胞在对IL-12作出反应时会产生IFN-γ，且不会有明显的组胺释放。在用2 U/ml重组小鼠IL-12培养6至24小时的肥大细胞上清液中，通过酶联免疫吸附测定法（ELISA）检测到了IFN-γ蛋白。IFN-γ的产生取决于IL-12的剂量，并被同时用IL-10或前列腺素E2（PGE2）处理显著抑制。IL-12刺激的肥大细胞的上清液通过IFN-γ依赖性机制诱导小鼠上皮细胞系MODE-K上的主要组织相容性复合体II类（MHC II）表达。在用抗IgE或LPS激活后培养的腹膜肥大细胞中，在能诱导产生IL-6的条件下，未检测到IFN-γ蛋白产生。我们得出结论，肥大细胞能够对IL-12产生IFN-γ反应，但肥大细胞大量产生IFN-γ并非IgE介导的激活所致。这些观察结果对于肥大细胞在局部免疫调节中的作用具有重要意义。
