"Eat me" signals of apoptotic bodies
"Eat me" signals of apoptotic bodies
复制标题
凋亡体的 "吃我 "信号
DOI：
10.1038/35014098
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发表时间：
2000-06-01
影响因子：
21.3
通讯作者：
Depraetere, V
中科院分区：
文献类型：
--
作者：
Depraetere, V
凋亡性细胞死亡的特征之一是细胞尸体被巨噬细胞或非专职吞噬细胞迅速清除。这是因为细胞凋亡的诱导导致在细胞溶解的晚期凋亡事件之前在细胞表面上暴露”吃我”信号。因此，细胞凋亡是一个“干净”的过程，通常不会导致细胞内容物溢出或炎症。暴露的磷脂酰丝氨酸（PS）残基，这是正常的不对称分布，并限制在质膜的内小叶，已被确定为细胞凋亡的早期事件和吞噬的先决条件，因为含PS的脂质体可以抑制吞噬凋亡小体。但是吞噬细胞上PS的受体是什么？虽然有几种细胞表面分子被认为有助于识别凋亡细胞，但它们似乎都不与PS残基特异性结合。另一种模型是识别基于嗜同性相互作用，因为最近报道了吞噬需要PS暴露在凋亡细胞和吞噬细胞的表面上（Marguet et al.，1，454-456; 1999）。现在，在最近一期的《自然》杂志（405，85-90; 2000）中，位于科罗拉多丹佛的国家犹太医学和研究中心的Valerie Fadok和同事们报道了利用针对活化的巨噬细胞的抗体克隆PS受体（PSR），他们发现这种抗体可以抑制凋亡细胞的吞噬。PSR在巨噬细胞和某些上皮细胞和成纤维细胞上表达。编码PSR的基因的转染赋予T和B细胞识别和吞噬凋亡细胞的能力，其被抗PSR抗体和含PS的脂质体抑制。图片显示了用编码PSR的互补DNA转染的3 T3成纤维细胞（标记为绿色），延伸突起并吞噬已被紫外线照射诱导死亡的Jurkat T细胞（标记为红色）。有趣的是，PSR基因在秀丽隐杆线虫和果蝇中是保守的，这表明，与凋亡程序的情况一样，吞噬机制可能在进化上是保守的。
One of the characteristics of apoptotic cell death is the rapid removal of cell corpses, which are engulfed by macrophages or by non-professional phagocytes. This is because induction of cell apoptosis leads to the exposure of" eat me" signals on the cell surface before the late apoptotic event of cell lysis. Thus, apoptosis is a ‘clean’process that does not normally lead to spillage of cell contents or to inflammation. Exposure of phosphatidylserine (PS) residues, which are normally asymmetrically distributed and restricted to the inner leaflet of the plasma membrane, has been identified as both an early event in apoptosis and a prerequisite for engulfment, as PS-containing liposomes can inhibit phagocytosis of apoptotic bodies. But what is the receptor for PS on phagocytic cells? Although several cell-surface molecules were proposed to contribute to the recognition of apoptotic cells, none of them seems to bind specifically to PS residues. An alternative model is that recognition is based on homophilic interactions, as exposure of PS on the surfaces of both apoptotic and phagocytic cells has recently been reported to be required for engulfment (Marguet et al., Nature Cell Biol. 1, 454–456; 1999). Now, in a recent issue of Nature (405, 85–90; 2000), Valerie Fadok and colleagues at the National Jewish Medical and Research Center in Denver, Colorado report the cloning of a PS receptor (PSR), using an antibody raised against activated macrophages, which they found to inhibit engulfment of apoptotic cells. PSR is expressed on macrophages and on certain epithelial cells and fibroblasts. Transfection of the gene encoding PSR confers T and B cells with the capacity to recognize and engulf apoptotic cells, which is inhibited by anti-PSR antibodies and by PS-containing liposomes. The picture shows a 3T3 fibroblast (labelled in green), transfected with complementary DNA encoding PSR, extending a protrusion and engulfing a Jurkat T cell that has been induced to die by ultraviolet irradiation (labelled in red). Interestingly, the PSR gene is conserved in Caenorhabditis elegans and Drosophila, indicating that, as is the case for the apoptotic programme, the mechanisms of engulfment may be evolutionarily conserved.