Iversen P O, Robinson D, Ying S, Meng Q, Kay A B, Clark-Lewis I, Lopez A F
Division of Human Immunology, Hanson Centre for Cancer Research, Adelaide, Australia.
Am J Respir Crit Care Med. 1997 Nov;156(5):1628-32. doi: 10.1164/ajrccm.156.5.9612097.
There is evidence that eosinophils have an important role in the pathogenesis of allergy and asthma. These cells are regulated by two classes of polypeptides, the colony-stimulating factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), and the chemokines, such as RANTES and eotaxin. GM-CSF is involved in the production, survival, and functional activation of eosinophils. RANTES and eotaxin regulate the migration of eosinophils to inflammatory sites, but any effect of these chemokines on eosinophil survival is not known. In this study we demonstrate that although GM-CSF promoted eosinophil survival, the specific GM-CSF analogue E21R induced apoptosis of eosinophils. Apoptosis was observed with unstimulated as well as with chemokine (RANTES and eotaxin)-activated eosinophils. Neither RANTES nor eotaxin supported eosinophil survival, and a RANTES antagonist did not affect either cell survival or apoptosis. E21R also induced apoptosis of eosinophils from asthmatic patients. These findings suggest that the GM-CSF receptor may actively control the death as well as the survival of eosinophils, and thus precisely regulate their numbers and activities. Our data also indicate that chemokines are not involved in regulating the lifespan of eosinophils. The introduction of the GM-CSF analogue E21R may offer a novel therapy in inflammatory diseases associated with eosinophil infiltration of different etiologies.
有证据表明，嗜酸性粒细胞在过敏和哮喘的发病机制中起重要作用。这些细胞受两类多肽调节，即集落刺激因子，如粒细胞-巨噬细胞集落刺激因子（GM-CSF），以及趋化因子，如RANTES和嗜酸性粒细胞趋化因子。GM-CSF参与嗜酸性粒细胞的产生、存活和功能激活。RANTES和嗜酸性粒细胞趋化因子调节嗜酸性粒细胞向炎症部位的迁移，但这些趋化因子对嗜酸性粒细胞存活的任何影响尚不清楚。在本研究中，我们证明，尽管GM-CSF可促进嗜酸性粒细胞存活，但特异性GM-CSF类似物E21R可诱导嗜酸性粒细胞凋亡。在未受刺激的嗜酸性粒细胞以及趋化因子（RANTES和嗜酸性粒细胞趋化因子）激活的嗜酸性粒细胞中均观察到凋亡。RANTES和嗜酸性粒细胞趋化因子均不支持嗜酸性粒细胞存活，且RANTES拮抗剂对细胞存活或凋亡均无影响。E21R还可诱导哮喘患者的嗜酸性粒细胞凋亡。这些发现表明，GM-CSF受体可能积极控制嗜酸性粒细胞的死亡以及存活，从而精确调节其数量和活性。我们的数据还表明，趋化因子不参与调节嗜酸性粒细胞的寿命。GM-CSF类似物E21R的引入可能为与不同病因嗜酸性粒细胞浸润相关的炎症性疾病提供一种新的治疗方法。
