Meagher L C, Cousin J M, Seckl J R, Haslett C
Rayne Laboratories, University Medical School, Edinburgh, United Kingdom.
J Immunol. 1996 Jun 1;156(11):4422-8.
Eosinophils and neutrophils are closely related, terminally differentiated cells that in vitro undergo constitutive cell death by apoptosis. The onset of apoptosis in both cell types can be delayed by hemopoietins and inflammatory mediators. Although there have been a number of reports demonstrating that glucocorticoids (in particular dexamethasone) antagonize the eosinophil life-prolonging effects of hemopoietins, direct effects of dexamethasone on eosinophil apoptosis have not been documented. In this study we examined the direct effects of glucocorticoids on eosinophil and neutrophil apoptosis in light of their common therapeutic use as anti-inflammatory and anti-allergic/hypereosinophilic agents. We found that treatment with dexamethasone induced eosinophil apoptosis. In contrast, dexamethasone was a potent inhibitor of neutrophil apoptosis. The effect of dexamethasone on both cell types was mediated through the glucocorticoid receptor, i.e., it was abolished by the glucocorticoid receptor antagonist RU38486. This is the first description of an agent that promotes eosinophil apoptosis while inhibiting neutrophil apoptosis, and thus presents a novel approach to the study of control of apoptosis in these closely related cell types as well as increases our understanding of the clinical action of glucocorticoids in inflammation.
嗜酸性粒细胞和中性粒细胞是密切相关的终末分化细胞，在体外会通过凋亡发生程序性细胞死亡。这两种细胞类型的凋亡起始可被造血因子和炎症介质延迟。尽管已有许多报告表明糖皮质激素（特别是地塞米松）可拮抗造血因子对嗜酸性粒细胞的寿命延长作用，但地塞米松对嗜酸性粒细胞凋亡的直接作用尚未见文献记载。在本研究中，鉴于糖皮质激素作为抗炎和抗过敏/高嗜酸性粒细胞血症药物的常见治疗用途，我们研究了其对嗜酸性粒细胞和中性粒细胞凋亡的直接作用。我们发现，地塞米松处理可诱导嗜酸性粒细胞凋亡。相反，地塞米松是中性粒细胞凋亡的强效抑制剂。地塞米松对这两种细胞类型的作用均通过糖皮质激素受体介导，即糖皮质激素受体拮抗剂RU38486可消除该作用。这是首次描述一种既能促进嗜酸性粒细胞凋亡又能抑制中性粒细胞凋亡的药物，因此为研究这些密切相关细胞类型中凋亡的调控提供了一种新方法，也增进了我们对糖皮质激素在炎症中临床作用的理解。
