Bandeira-Melo C, Sugiyama K, Woods L J, Weller P F
Department of Medicine, Harvard Thorndike Laboratories, Charles A. Dana Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Immunol. 2001 Apr 15;166(8):4813-7. doi: 10.4049/jimmunol.166.8.4813.
IL-4 release is important in promoting Th2-mediated allergic and parasitic immune responses. Although human eosinophils are potential sources of IL-4, physiologic mechanisms to elicit its release have not been established. By flow cytometry and microscopy, eosinophils from normal donors uniformly contained preformed IL-4. In contrast to cytolytic IL-4 release from calcium ionophore-activated eosinophils, eotaxin and RANTES, but not IFN-gamma, elicited IL-4 release by noncytotoxic mechanisms. With a dual Ab capture and detection immunofluorescent microscopic assay, IL-4 was released at discrete cell surface sites. IL-5 enhanced eotaxin-induced IL-4 release, which was mediated by G protein-coupled CCR3 receptors, detectable as early as 5 min and maximum within 1 h. IL-4 release was not diminished by transcription or protein synthesis inhibitors, but was suppressed by brefeldin A, an inhibitor of vesicle formation. Thus, CCR3-mediated signaling can rapidly mobilize IL-4 stored preformed in human eosinophils for release by vesicular transport to contribute to immune responses.
白细胞介素-4（IL-4）的释放对于促进Th2介导的过敏和寄生虫免疫反应至关重要。虽然人类嗜酸性粒细胞是IL-4的潜在来源，但其释放的生理机制尚未明确。通过流式细胞术和显微镜检查发现，正常供体的嗜酸性粒细胞均含有预先形成的IL-4。与钙离子载体激活的嗜酸性粒细胞溶细胞性释放IL-4不同，嗜酸性粒细胞趋化因子（eotaxin）和RANTES而非干扰素-γ（IFN-γ）通过非细胞毒性机制引发IL-4释放。采用双抗体捕获和检测免疫荧光显微镜检测法，发现IL-4在离散的细胞表面位点释放。白细胞介素-5（IL-5）增强了嗜酸性粒细胞趋化因子诱导的IL-4释放，这是由G蛋白偶联的CCR3受体介导的，最早在5分钟时即可检测到，1小时内达到最大值。转录或蛋白质合成抑制剂不会减少IL-4的释放，但囊泡形成抑制剂布雷菲德菌素A（brefeldin A）可抑制其释放。因此，CCR3介导的信号传导可迅速动员人类嗜酸性粒细胞中预先形成并储存的IL-4，通过囊泡运输释放，从而有助于免疫反应。
