Burd P R, Thompson W C, Max E E, Mills F C
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20592, USA.
J Exp Med. 1995 Apr 1;181(4):1373-80. doi: 10.1084/jem.181.4.1373.
When mast cells are activated through their immunoglobulin (Ig)E receptors, release of low molecular weight mediators like histamine is followed by secretion of multiple cytokines, including interleukin (IL)-3, IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor. Here we report that stimulated mast cells also synthesize IL-13 mRNA and protein; secretion of this cytokine may be of particular importance because of its ability to stimulate IgE expression. IL-13 transcripts detected by a semiquantitative reverse transcriptase-mediated polymerase chain reaction assay were induced within 30 min after stimulation of mast cells by dinitrophenyl plus monoclonal IgE anti-dinitrophenyl, and peaked at about 1 h. Within 3 h of IgE stimulation, secreted IL-13 bioactivity, estimated by proliferation of an IL-13-dependent cell line, reached levels equivalent to 1-2 ng/ml of IL-13. When added to human B lymphocytes, the mast cell-derived IL-13 activity (like bone fide IL-13) induced Ig C epsilon transcripts, DNA recombination characteristic of the isotype switch to C epsilon, and the secretion of IgE protein. These results suggest a model of local positive feedback interactions between mast cells and B cells, which could play a role in the pathogenesis of atopy.
当肥大细胞通过其免疫球蛋白(Ig)E受体被激活时,在释放组胺等低分子量介质之后,会分泌多种细胞因子,包括白细胞介素(IL)-3、IL-4、IL-5以及粒细胞/巨噬细胞集落刺激因子。在此我们报告,受刺激的肥大细胞还能合成IL-13 mRNA和蛋白;这种细胞因子的分泌可能尤为重要,因为它能够刺激IgE表达。通过半定量逆转录酶介导的聚合酶链反应检测到的IL-13转录本,在二硝基苯基加抗二硝基苯基单克隆IgE刺激肥大细胞后30分钟内被诱导产生,并在约1小时时达到峰值。在IgE刺激后3小时内,通过IL-13依赖细胞系的增殖估算的分泌型IL-13生物活性达到了相当于1 - 2 ng/ml IL-13的水平。当将肥大细胞衍生的IL-13活性(如同真正的IL-13)添加到人B淋巴细胞中时,会诱导Ig Cε转录本、向Cε同种型转换的DNA重组特征以及IgE蛋白的分泌。这些结果提示了肥大细胞与B细胞之间局部正反馈相互作用的模型,这可能在特应性疾病的发病机制中发挥作用。