Woerly Gaetane, Lacy Paige, Younes Amena Ben, Roger Nadine, Loiseau Sylvie, Moqbel Redwan, Capron Monique
Centre d'Immunologie et Biologie Parasitaire, Unité INSERM U547 and IFR17, Institut Pasteur, Lille, France.
J Leukoc Biol. 2002 Oct;72(4):769-79.
Human eosinophils produce a large number of cytokines, including immunoregulatory cytokines. Given that eosinophils store and release interleukin (IL)-4, a key cytokine in the pathogenesis of allergic inflammation, and that IL-4 and IL-13 share common biological functions, we investigated the possibility that IL-13 may be synthesized by these cells. Using flow cytometry and immunocytochemistry, we show that eosinophils synthesize and store IL-13. Granule localization was demonstrated after subcellular fractionation, and IL-13 immunoreactivity was localized to crystalloid, granule-enriched fractions. Furthermore, electron microscopic analyses specifically localized IL-13 to the dense cores of bicompartmental secondary granules. Upon CD28 ligation, IL-13 was released by eosinophils, whereas a combination of CD28 and immunoglobulin A complexes resulted in decreased IL-13 secretion. Furthermore, eosinophil-derived IL-13 exerts a biological effect, inducing CD23 expression on B cells. By having the capacity to synthesize and release IL-13, eosinophils may participate in the development and maintenance of the T helper cell type 2 response, a prominent feature of allergic diseases.
人类嗜酸性粒细胞可产生大量细胞因子,包括免疫调节细胞因子。鉴于嗜酸性粒细胞储存并释放白细胞介素(IL)-4(过敏性炎症发病机制中的关键细胞因子),且IL-4和IL-13具有共同的生物学功能,我们研究了这些细胞合成IL-13的可能性。通过流式细胞术和免疫细胞化学方法,我们发现嗜酸性粒细胞可合成并储存IL-13。亚细胞分级分离后证实了颗粒定位,且IL-13免疫反应性定位于富含晶体和颗粒的组分中。此外,电子显微镜分析将IL-13特异性定位于双室次级颗粒的致密核心。CD28连接后,嗜酸性粒细胞释放IL-13,而CD28与免疫球蛋白A复合物的组合则导致IL-13分泌减少。此外,嗜酸性粒细胞衍生的IL-13具有生物学效应,可诱导B细胞上CD23的表达。由于具有合成和释放IL-13的能力,嗜酸性粒细胞可能参与2型辅助性T细胞反应的发生和维持,这是过敏性疾病的一个显著特征。