Martin S, Pombo I, Poncet P, David B, Arock M, Blank U
Unité Immuno-Allergie, Institut Pasteur, Paris, France.
Int Arch Allergy Immunol. 2000 Nov;123(3):249-58. doi: 10.1159/000024451.
Loss of phospholipid asymmetry represents one of the hallmarks of apoptosis and results in the surface exposure of phosphatidylserine (PS) which can be indirectly monitored by the calcium-dependent binding of annexin V.
Here, we provide evidence that the IgE-dependent stimulation of a rat mast cell line, as well as murine and human nontransformed mast cells, leads to the exposure of PS at the plasma membrane. The appearance of PS was quantitatively related to allergic mediator release. Pharmacological agents that prevent stimulus-secretion coupling blocked PS cell surface exposure and calcium ionophore-induced PS appearance, suggesting that it is a direct consequence of exocytosis rather than early signaling events initiated by the aggregation of the high-affinity IgE receptor (FcepsilonRI). The surface exposure of PS in mast cells was reversible even in the continuous presence of stimulus and was not associated with the appearance of apoptotic nuclei, demonstrating that it was independent of physiological cell death.
In addition to providing a means of monitoring exocytosis at the single cell level, our results indicate that PS externalization in mast cells is not necessarily related to apoptosis but could be an important feature of the degranulation process.
磷脂不对称性的丧失是细胞凋亡的标志之一，会导致磷脂酰丝氨酸（PS）暴露于细胞表面，这可以通过钙依赖性的膜联蛋白V结合来间接监测。
在此，我们提供证据表明，IgE依赖性刺激大鼠肥大细胞系以及小鼠和人类未转化的肥大细胞，会导致PS在质膜上暴露。PS的出现与过敏介质释放存在定量关系。阻止刺激-分泌偶联的药物可阻断PS在细胞表面的暴露以及钙离子载体诱导的PS出现，这表明它是胞吐作用的直接后果，而非由高亲和力IgE受体（FcepsilonRI）聚集引发的早期信号事件。肥大细胞中PS的表面暴露即使在持续存在刺激的情况下也是可逆的，并且与凋亡细胞核的出现无关，这表明它与生理性细胞死亡无关。
除了提供一种在单细胞水平监测胞吐作用的方法外，我们的结果表明肥大细胞中PS外化不一定与细胞凋亡相关，而可能是脱颗粒过程的一个重要特征。
