Fadeel Bengt, Quinn Peter, Xue Ding, Kagan Valerian
HFSP J. 2007 Nov;1(4):225-9. doi: 10.2976/1.2800110. Epub 2007 Oct 22.
Phagocytosis of apoptotic cell corpses is a conserved and well-regulated process and is required to maintain tissue homeostasis within an organism. Evidence suggests that apoptotic cell engulfment by macrophages is dependent upon the externalization of phosphatidylserine (PS) on the plasma membrane of the dying cell. Furthermore, oxidation of PS and other phospholipids may serve to facilitate cell corpse removal. However, our understanding of how these various lipid "eat-me" signals are recognized by macrophages has been limited. Using a combination of cellular and animal models, along with an array of biophysical methods, Hazen and his associates (Greenberg et al., J. Exp. Med., 2006, 203, 2613-2625;Li et al., Biochemistry, 2007, 46, 5009-5017) have now identified the scavenger receptor CD36 as a putative receptor for oxidized PS on apoptotic cells; moreover, they have deduced the conformation of the oxidized lipid ligand that is recognized by this receptor, thus providing structural insight into how phagocytes recognize senescent or apoptotic cells.
凋亡细胞尸体的吞噬作用是一个保守且调控良好的过程,是维持生物体内组织稳态所必需的。有证据表明,巨噬细胞对凋亡细胞的吞噬依赖于垂死细胞膜上磷脂酰丝氨酸(PS)的外化。此外,PS和其他磷脂的氧化可能有助于细胞尸体的清除。然而,我们对巨噬细胞如何识别这些各种脂质“吃我”信号的理解一直有限。通过结合细胞和动物模型以及一系列生物物理方法,哈森及其同事(格林伯格等人,《实验医学杂志》,2006年,203卷,2613 - 2625页;李等人,《生物化学》,2007年,46卷,5009 - 5017页)现已确定清道夫受体CD36是凋亡细胞上氧化PS的假定受体;此外,他们还推断出了该受体所识别的氧化脂质配体的构象,从而为吞噬细胞如何识别衰老或凋亡细胞提供了结构上的见解。