Fas-mediated apoptosis in cultured human eosinophils
Fas-mediated apoptosis in cultured human eosinophils
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DOI：
10.1182/blood.v87.7.2822.bloodjournal8772822
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发表时间：
1996-04-01
期刊：
影响因子：
20.3
通讯作者：
Pretolani, M
中科院分区：
文献类型：
--
作者：
Druilhe, A;Cai, ZZ;Pretolani, M
先前的研究表明，细胞因子剥夺的嗜酸性粒细胞发生凋亡，但控制这一现象的机制尚不清楚。Fas抗原是一种跨膜糖蛋白，属于肿瘤坏死因子受体家族。Fas抗原在多种细胞类型中的交联可导致细胞凋亡。在本研究中，我们研究了Fas抗原在健康供者纯化血嗜酸性粒细胞凋亡中的潜在作用。流式细胞术和逆转录聚合酶链反应分别显示，细胞因子剥夺的嗜酸性粒细胞表现出时间依赖性的活力丧失，同时凋亡细胞核数量增加，Fas抗原及其mRNA表达增加。Fas抗原与激动性抗Fas单克隆抗体（MoAb）交联诱导凋亡细胞核数量呈剂量和时间依赖性增加。此外，使用体外共培养系统，我们发现单核细胞来源的巨噬细胞吞噬抗fas moab处理的嗜酸性粒细胞。最后，将嗜酸性粒细胞与皮质类固醇、地塞米松一起培养，诱导细胞凋亡，并增强抗Fas MoAb触发的细胞凋亡。总之，这些观察结果表明，Fas抗原的表达和激活参与了人类嗜酸性粒细胞的凋亡，并可能有助于解决炎症性过敏反应，其中嗜酸性粒细胞积累是一个突出的特征。(C) 1996年由美国血液病学会出版。
Previous studies have shown that cytokine-deprived eosinophils undergo apoptosis, yet the mechanisms governing this phenomenon remain obscure. Fas antigen is a transmembrane glycoprotein belonging to the tumor necrosis factor receptor family. Cross-linking of Fas antigen in numerous cell types leads to apoptosis. In the present study, we examined the potential role of Fas antigen in the apoptosis of purified blood eosinophils from healthy donors. Cytokine-deprived eosinophils exhibited a time-dependent loss in viability, accompanied by an increase in the number of apoptotic nuclei and in the expression of Fas antigen and its mRNA, as shown by flow cytometry and reverse transcriptase-polymerase chain reaction, respectively. Crosslinking of Fas antigen with an agonistic anti-Fas mono-clonal antibody (MoAb) induced a dose- and time-dependent increase in the number of apoptotic nuclei. Furthermore, using an in vitro coculture system, we showed engulfment of anti-Fas MoAb-treated eosinophils by monocyte-derived macrophages. Finally, incubation of eosinophils with the corticosteroid, dexamethasone, induced apoptosis and augmented that triggered by anti-Fas MoAb, Together, these observations suggest that Fas antigen expression and activation is involved in the apoptosis of human eosinophils and may contribute to the resolution of inflammatory allergic reactions in which eosinophil accumulation is a prominent feature. (C) 1996 by The American Society of Hematology.