Druilhe A, Létuvé S, Pretolani M
Institut National de la Santé et de la Recherche Médicale (INSERM) U408, Faculté de Médecine Xavier Bichat, Paris, France.
Apoptosis. 2003 Oct;8(5):481-95. doi: 10.1023/a:1025590308147.
Prominent blood and tissue eosinophilia is clinically manifested in a number of inflammatory states, particularly in allergic diseases. Corticosteroids are the most effective anti-inflammatory drugs used in the treatment of eosinophilic disorders, including bronchial asthma. Their beneficial effects result, among others, from (i) the suppression of the synthesis and the effects of eosinophil survival factors, (ii) the direct induction of eosinophil apoptosis and (iii) the stimulation of their engulfment by professional phagocytic cells. Failure of steroids to propagate apoptotic signals and to promote eosinophil clearance may explain the corticoresistance observed in a proportion of asthmatic patients. Accordingly, studies on the intracellular mechanisms involved in eosinophil corticosensitivity and resistance may provide a valuable tool for identifying new and selective molecular targets to therapeutically resolve otherwise persistent eosinophilic inflammation. In this review, the intracellular cascade of events involved in corticosteroid-mediated eosinophil apoptotic death is discussed and compared to the signalling pathway governing this process in the established model of dexamethasone-induced thymocyte apoptosis.
显著的血液和组织嗜酸性粒细胞增多在多种炎症状态中都有临床表现，尤其是在过敏性疾病中。皮质类固醇是用于治疗嗜酸性粒细胞疾病（包括支气管哮喘）的最有效的抗炎药物。它们的有益作用尤其源于：（i）抑制嗜酸性粒细胞存活因子的合成及其作用；（ii）直接诱导嗜酸性粒细胞凋亡；（iii）刺激专业吞噬细胞对嗜酸性粒细胞的吞噬作用。类固醇未能传递凋亡信号并促进嗜酸性粒细胞清除，这可能解释了一部分哮喘患者中观察到的皮质激素抵抗现象。因此，对嗜酸性粒细胞皮质激素敏感性和抵抗所涉及的细胞内机制的研究，可能为识别新的选择性分子靶点提供有价值的工具，从而在治疗上解决持续存在的嗜酸性粒细胞炎症。在这篇综述中，我们将讨论皮质类固醇介导的嗜酸性粒细胞凋亡死亡所涉及的细胞内事件级联反应，并将其与地塞米松诱导胸腺细胞凋亡的既定模型中控制这一过程的信号通路进行比较。
