Hsieh Chia-Wei, Lan Joung-Liang, Meng Qiu, Cheng Ya-Wen, Huang Huei-Mei, Tsai Jaw-Ji
Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
J Formos Med Assoc. 2007 Jan;106(1):36-43. doi: 10.1016/S0929-6646(09)60214-X.
BACKGROUND/PURPOSE: Eosinophils are important effector cells in the pathogenesis of allergic bronchial asthma. Enhancement of eosinophil apoptosis has been considered to have therapeutic effect on allergic disease. Fungal immunomodulatory peptide (FIP)-fve has been reported to possess immunoprophylactic activities for allergic diseases. The purpose of this study was to investigate the modulation of FIP-fve on human eosinophil survival derived from allergic asthmatic patients.
Eosinophils were obtained from allergic asthmatic patients and purified with the use of density gradients and immunomagnetic beads negative selection. Apoptosis was assessed by annexin V and propidium iodide. The apoptotic signal protein, CD95 and IL-5 receptor expression were assessed by Western blot and flow cytometric analysis.
When the eosinophils were treated with FIP-fve in the presence of IL-5, IL-5-enhanced eosinophil survival diminished. FIP-fve could reduce IL-5-mediated survival of eosinophils and decrease IL-5Ralpha expression. In the presence of FIP-fve, CD95 expression was upregulated and Bcl-xL and pro-caspase 3 expression were downregulated in cultured eosinophils.
The results suggest that FIP-fve can inhibit IL-5-mediated survival of eosinophils through the modulation of cytokine receptor expression and apoptotic signal protein production. The modulatory effect of FIP-fve on eosinophil apoptosis in vitro indicates that it may have some therapeutic effect on eosinophil-related allergic inflammation in vivo.
背景/目的：嗜酸性粒细胞是过敏性支气管哮喘发病机制中的重要效应细胞。增强嗜酸性粒细胞凋亡被认为对过敏性疾病具有治疗作用。据报道，真菌免疫调节肽（FIP）-fve对过敏性疾病具有免疫预防活性。本研究的目的是探讨FIP-fve对过敏性哮喘患者来源的人嗜酸性粒细胞存活的调节作用。
从过敏性哮喘患者中获取嗜酸性粒细胞，并通过密度梯度和免疫磁珠阴性选择进行纯化。通过膜联蛋白V和碘化丙啶评估凋亡情况。通过蛋白质免疫印迹法和流式细胞术分析评估凋亡信号蛋白、CD95和白细胞介素-5受体的表达。
当嗜酸性粒细胞在白细胞介素-5存在的情况下用FIP-fve处理时，白细胞介素-5增强的嗜酸性粒细胞存活能力减弱。FIP-fve可降低白细胞介素-5介导的嗜酸性粒细胞存活，并降低白细胞介素-5Rα的表达。在FIP-fve存在的情况下，培养的嗜酸性粒细胞中CD95表达上调，Bcl-xL和前半胱天冬酶3表达下调。
结果表明，FIP-fve可通过调节细胞因子受体表达和凋亡信号蛋白产生来抑制白细胞介素-5介导的嗜酸性粒细胞存活。FIP-fve在体外对嗜酸性粒细胞凋亡的调节作用表明，它可能对体内嗜酸性粒细胞相关的过敏性炎症具有一定的治疗作用。
