Bevers E M, Comfurius P, Dekkers D W, Harmsma M, Zwaal R F
Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Lupus. 1998;7 Suppl 2:S126-31. doi: 10.1177/096120339800700228.
The various phospholipid classes that comprise mammalian cell membranes are distributed over both leaflets of the bilayer in a non-random fashion. While a specific and ATP-dependent transporter is responsible for rapid inward movement of aminophospholipids, its inhibition does not lead to spontaneous redistribution of lipids. Conditions of cellular activation which are accompanied with increased levels of intracellular Ca2+ may cause a collapse of lipid asymmetry by switching on an ATP-independently operating scramblase, which accelerates bidirectional movement of all phospholipid classes. The most prominent change in transmembrane lipid distribution is surface exposure of phosphatidylserine (PS), the more so since conditions which activate scramblase in most if not all cases lead to inhibition of aminophospholipid translocase activity, which will prevent PS from being pumped back to the inner leaflet of the membrane. Surface-exposed PS serves at least two important physiological functions: it promotes blood coagulation and offers a recognition signal for clearance by macrophages and other cells of the reticuloendothelial system. As such, PS exposure may form an important early event in the process of apoptosis to ensure rapid removal of these cells in order to avoid release of their inflammatory contents. Defective regulation of transbilayer lipid distribution may result in clinical manifestations such as in the Scott syndrome, a bleeding disorder caused by an impaired scramblase activity. Conversely, excessive PS exposure may lead to thrombosis or may explain formation of so-called antiphospholipid antibodies as occurring in patients with antiphospholipid syndrome.
构成哺乳动物细胞膜的各种磷脂类以非随机方式分布在双层膜的两个小叶上。虽然一种特定的、依赖ATP的转运蛋白负责氨基磷脂的快速内向移动，但其抑制并不会导致脂质的自发重新分布。伴随着细胞内Ca2+水平升高的细胞激活条件可能会通过开启一种不依赖ATP运行的磷脂翻转酶而导致脂质不对称性的崩溃，该酶会加速所有磷脂类的双向移动。跨膜脂质分布最显著的变化是磷脂酰丝氨酸（PS）暴露于表面，尤其是因为在大多数（如果不是全部）情况下激活磷脂翻转酶的条件会导致氨基磷脂转位酶活性受到抑制，这将阻止PS被泵回膜的内小叶。表面暴露的PS至少具有两种重要的生理功能：它促进血液凝固，并为巨噬细胞和网状内皮系统的其他细胞提供清除的识别信号。因此，PS暴露可能是细胞凋亡过程中的一个重要早期事件，以确保这些细胞被快速清除，从而避免其炎症内容物的释放。跨膜脂质分布调节缺陷可能导致临床表现，如斯科特综合征，这是一种由磷脂翻转酶活性受损引起的出血性疾病。相反，过度的PS暴露可能导致血栓形成，或者可以解释抗磷脂综合征患者中出现的所谓抗磷脂抗体的形成。
