Simon Hans-Uwe
Institute of Pharmacology, University of Bern, Bern, Switzerland.
Apoptosis. 2009 Apr;14(4):439-46. doi: 10.1007/s10495-008-0299-1.
Apoptosis, the most common form of cell death, is a key mechanism in the build up and maintenance of both innate and adaptive immunity. Central to the apoptotic process is a family of intracellular cysteine proteases with aspartate-specificity, called caspases. Caspases are counter-regulated by multiple anti-apoptotic molecules, and the expression of the latter in leukocytes is largely dependent on survival factors. Therefore, the physiologic rates of apoptosis change under pathologic conditions. For instance, in inflammation, the expression of survival factors is usually elevated, resulting in increased cell survival and consequently in the accumulation of the involved immune cells. In many allergic diseases, eosinophil apoptosis is delayed contributing to both blood and tissue eosinophilia. Besides eosinophils, apoptosis of other leukocytes is also frequently prevented or delayed during allergic inflammatory processes. In contrast to inflammatory cells, accelerated cell death is often observed in epithelial cells, a mechanism, which amplifies or at least maintains allergic inflammation. In conclusion, deregulated cell death is a common phenomenon of allergic diseases that likely plays an important role in their pathogenesis. Whether the apoptosis is too little or too much depends on the cell type. In this review, we discuss the regulation of the lifespan of the participating leukocytes in allergic inflammatory responses.
细胞凋亡是最常见的细胞死亡形式，是固有免疫和适应性免疫建立与维持的关键机制。细胞凋亡过程的核心是一类具有天冬氨酸特异性的细胞内半胱氨酸蛋白酶家族，称为半胱天冬酶。半胱天冬酶受到多种抗凋亡分子的反向调节，而后者在白细胞中的表达很大程度上依赖于生存因子。因此，细胞凋亡的生理速率在病理条件下会发生变化。例如，在炎症中，生存因子的表达通常会升高，导致细胞存活率增加，进而导致相关免疫细胞的积累。在许多过敏性疾病中，嗜酸性粒细胞凋亡延迟，导致血液和组织嗜酸性粒细胞增多。除了嗜酸性粒细胞外，在过敏性炎症过程中，其他白细胞的凋亡也经常被阻止或延迟。与炎症细胞相反，上皮细胞中经常观察到细胞死亡加速，这是一种放大或至少维持过敏性炎症的机制。总之，细胞死亡失调是过敏性疾病的常见现象，可能在其发病机制中起重要作用。细胞凋亡是过少还是过多取决于细胞类型。在这篇综述中，我们讨论了过敏性炎症反应中参与的白细胞寿命的调节。
