Eosinophils from Asthmatics Release IL-5 in an Autocrine Fashion to Prevent Apoptosis Through Upregulation of Bcl-2 Expression
Eosinophils from Asthmatics Release IL-5 in an Autocrine Fashion to Prevent Apoptosis Through Upregulation of Bcl-2 Expression
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DOI：
10.1081/jas-63001
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发表时间：
2005-01
影响因子：
1.9
通讯作者：
Chien-Da Huang;Chun-Hua Wang;Chien‐Ying Liu;Shu-Min Lin;C. Chou;Wen-Te Liu;Horng-Chyuan Lin;H. Kuo
中科院分区：
文献类型：
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作者：
Chien-Da Huang;Chun-Hua Wang;Chien‐Ying Liu;Shu-Min Lin;C. Chou;Wen-Te Liu;Horng-Chyuan Lin;H. Kuo
白细胞介素5（IL-5）通过其受体的特异性α亚基在维持嗜酸性粒细胞存活中发挥重要作用。细胞凋亡是细胞程序性死亡的一种形式，被认为是促进哮喘嗜酸性粒细胞炎症消退的一种机制。本研究的目的是探讨IL-5是否以自分泌方式对哮喘患者嗜酸性粒细胞凋亡起作用。细胞内IL-5和IL-5受体α亚单位（Rα）的免疫反应性仅在嗜酸性粒细胞上检测到。流式细胞术检测哮喘患者嗜酸粒细胞IL-5和IL-5 Rα表达水平明显高于正常对照组（P < 0.05）。碘化丙啶染色法和DNA梯状条带法检测嗜酸性粒细胞凋亡。与相应的对照组相比，哮喘患者的嗜酸性粒细胞凋亡百分比在与抗hIL-5 Rα Ab（0.1、0.5和2.5 μg/mL）共孵育1、2或16小时后显著增加（p < 0.05，n = 8）。而抗hIL-5 Rα Ab对正常人嗜酸性粒细胞凋亡无明显影响。抗hIL-5 Rα Ab或反义IL-5寡核苷酸可显著抑制哮喘患者外周血B细胞淋巴瘤2（Bcl-2）蛋白的表达（p < 0.05，n = 8），但对正常人外周血嗜酸性粒细胞的表达无明显影响。本研究表明，哮喘患者的嗜酸性粒细胞以自分泌方式释放IL-5，作用于其自身的IL-5受体，通过上调Bcl-2的表达来防止细胞凋亡。
Interleukin (IL)-5 plays an important role in maintaining the survival of eosinophils via the specific α-subunit of its receptor. Apoptosis, a form of programmed cell death, is thought to represent a mechanism that promotes the resolution of eosinophilic inflammation in asthma. The aim of our present study is to investigate whether IL-5 acts in an autocrine fashion on eosinophil apoptosis in asthmatics. Immunoreactivities of intracellular IL-5 and IL-5 receptor α-subunit (Rα) were detected uniquely on the eosinophils. The magnitude of IL-5 and IL-5 Rα expression on eosinophils was significantly higher in asthmatics than that of normal subjects (p < 0.05) determined by flow cytometry. Apoptosis of eosinophils was measured by the propidium iodide staining method and DNA ladder. The percent of apoptotic eosinophils from asthmatics was significantly increased by coincubation with anti-hIL-5 Rα Ab (0.1, 0.5, and 2.5 µg/mL) for 1, 2, or 16 hours than was those of corresponding controls (p < 0.05, n = 8). However, there was no significant effect of anti-hIL-5 Rα Ab on eosinophil apoptosis in normal subjects. Furthermore, the expression of B-cell lymphoma-2 (Bcl-2) proteins was significantly inhibited by the anti-hIL-5 Rα Ab or antisense IL-5 oligonucleotides in asthmatics (p < 0.05, n = 8), but there was no significant change in eosinophils from normal subjects. This study demonstrates that eosinophils from asthmatics release IL-5 in an autocrine fashion to act on their own IL-5 receptors in prevention of apoptosis through the upregulation of Bcl-2 expression.