Murphy Finbarr J, Hayes Ian, Cotter Thomas G
Eirx Therapeutics Ltd, 2800 Cork Airport Business Park, Kinsale Road, Cork, Ireland.
Curr Opin Pharmacol. 2003 Aug;3(4):412-9. doi: 10.1016/s1471-4892(03)00072-9.
Induction of apoptosis in immune cells is a crucial mechanism used by the body to produce immune resolution. The homeostatic mechanisms employed are currently being identified and, to date, studies have highlighted some of the signals that regulate the immune response. The exposure of phosphatidylserine on the surface of an apoptotic neutrophil is sufficient to limit the immune response in acute inflammation, whereas apoptosis of key effector cells can limit the response in chronic inflammation. Other therapeutic approaches that are being investigated include the inhibition of apoptosis by blocking the caspase cascade. This approach will be of particular relevance for the treatment of inflammatory central nervous system diseases and sepsis. An alternative approach being examined is forced resolution, whereby apoptosis is induced in effector cells, principally T cells, through activation-induced cell death mediated by Fas receptors. Inhibitors of this mechanism have been identified and targeted in several studies.
免疫细胞凋亡的诱导是机体实现免疫消退的关键机制。目前正在确定所采用的稳态机制，迄今为止，研究已经突出了一些调节免疫反应的信号。凋亡中性粒细胞表面磷脂酰丝氨酸的暴露足以限制急性炎症中的免疫反应，而关键效应细胞的凋亡则可限制慢性炎症中的反应。正在研究的其他治疗方法包括通过阻断半胱天冬酶级联反应来抑制细胞凋亡。这种方法对于治疗炎症性中枢神经系统疾病和脓毒症将具有特别重要的意义。正在研究的另一种方法是强制消退，即通过由Fas受体介导的激活诱导的细胞死亡，在效应细胞（主要是T细胞）中诱导凋亡。在几项研究中已经鉴定并靶向了这种机制的抑制剂。
