Hebestreit H, Yousefi S, Balatti I, Weber M, Crameri R, Simon D, Hartung K, Schapowal A, Blaser K, Simon H U
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
Eur J Immunol. 1996 Aug;26(8):1775-80. doi: 10.1002/eji.1830260817.
The interaction between activated T cells and eosinophils has been proposed to play an important role in the pathogenesis of allergic diseases. T cell-derived cytokines such as interleukin-5 and granulocyte/macrophage colony-stimulating factor inhibit eosinophil apoptosis and may therefore contribute to the development of tissue and blood eosinophilia in these disorders. Withdrawal of these cytokines leads to eosinophil apoptosis in vitro. In contrast, the mechanisms which actively induce apoptosis in eosinophils are at present not completely understood. In this study, we demonstrate that freshly isolated human eosinophils express mRNA and protein for the Fas receptor. Using anti-Fas monoclonal antibody (mAb), we show that Fas activation accelerates apoptotic eosinophil death in vitro. Moreover, treatment of nasal polyps ex vivo with anti-Fas mAb decreased eosinophilic tissue inflammation. However, we observed that blood as well as tissue eosinophils derived from some eosinophilic donors do not express functional Fas receptors, although Fas protein is normally expressed in these cells. This implies that the susceptibility of the Fas receptor is a matter of regulation in eosinophils as previously observed in other systems. These data suggest that Fas ligand/Fas interactions are involved in the regulation of eosinophil apoptosis and that defects in this system could contribute to the accumulation of these cells in allergic and asthmatic diseases.
活化T细胞与嗜酸性粒细胞之间的相互作用被认为在过敏性疾病的发病机制中起重要作用。T细胞衍生的细胞因子如白细胞介素-5和粒细胞/巨噬细胞集落刺激因子可抑制嗜酸性粒细胞凋亡，因此可能在这些疾病中导致组织和血液嗜酸性粒细胞增多。去除这些细胞因子会导致体外嗜酸性粒细胞凋亡。相反，目前对嗜酸性粒细胞中主动诱导凋亡的机制尚未完全了解。在本研究中，我们证明新鲜分离的人嗜酸性粒细胞表达Fas受体的mRNA和蛋白。使用抗Fas单克隆抗体（mAb），我们表明Fas激活可加速体外嗜酸性粒细胞的凋亡死亡。此外，用抗Fas mAb离体处理鼻息肉可减轻嗜酸性粒细胞组织炎症。然而，我们观察到，尽管Fas蛋白通常在这些细胞中表达，但来自一些嗜酸性粒细胞供体的血液和组织嗜酸性粒细胞不表达功能性Fas受体。这意味着Fas受体的敏感性是嗜酸性粒细胞中的一个调节问题，正如先前在其他系统中所观察到的。这些数据表明Fas配体/Fas相互作用参与嗜酸性粒细胞凋亡的调节，并且该系统中的缺陷可能导致这些细胞在过敏性和哮喘性疾病中的积聚。
