Matsumoto K, Schleimer R P, Saito H, Iikura Y, Bochner B S
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224-6801, USA.
Blood. 1995 Aug 15;86(4):1437-43.
Fas antigen (CD95) can induce apoptosis of cells such as lymphocytes and neutrophils. To determine whether Fas antigen is involved in eosinophil apoptosis, we examined its expression and function on eosinophils in vitro. Purified human eosinophils expressed low but consistently detectable levels of Fas antigen. Culture of eosinophils in up to 10 ng/mL interleukin-5 (IL-5) prolonged eosinophil survival; incorporation of 1 to 1,000 ng/mL Fas antibody led to significant reductions in IL-5-induced eosinophil viability after 48 to 72 hours of culture. Reductions in survival could not be overcome by IL-5 and also occurred in the absence of exogenous IL-5. Preactivation of eosinophils with platelet-activating factor (PAF) significantly reduced eosinophil viability without altering the survival-reducing effects of Fas antibody treatment. In contrast, RANTES did not affect eosinophil viability or Fas antibody-induced reductions in eosinophil survival. After treatment with Fas antibody, electron microscopy of eosinophils and gel electrophoresis of DNA extracted from eosinophils demonstrated changes consistent with apoptosis. These data demonstrate that Fas antigen can modify eosinophil survival by inducing apoptosis through a pathway that is, at least in part, independent of the survival-promoting effects of IL-5.
Fas抗原（CD95）可诱导淋巴细胞和中性粒细胞等细胞发生凋亡。为确定Fas抗原是否参与嗜酸性粒细胞凋亡，我们在体外检测了其在嗜酸性粒细胞上的表达及功能。纯化的人嗜酸性粒细胞表达低水平但始终可检测到的Fas抗原。在高达10 ng/mL的白细胞介素-5（IL-5）中培养嗜酸性粒细胞可延长其存活时间；加入1至1000 ng/mL的Fas抗体，在培养48至72小时后可导致IL-5诱导的嗜酸性粒细胞活力显著降低。IL-5无法克服存活时间的缩短，且在无外源性IL-5的情况下也会发生。用血小板活化因子（PAF）预激活嗜酸性粒细胞可显著降低其活力，但不改变Fas抗体处理对存活的降低作用。相比之下，RANTES不影响嗜酸性粒细胞活力或Fas抗体诱导的嗜酸性粒细胞存活时间缩短。用Fas抗体处理后，嗜酸性粒细胞的电子显微镜检查及从嗜酸性粒细胞中提取的DNA的凝胶电泳显示出与凋亡一致的变化。这些数据表明，Fas抗原可通过诱导凋亡来改变嗜酸性粒细胞的存活，该途径至少部分独立于IL-5的促存活作用。
