Schlegel R A, Callahan M, Krahling S, Pradhan D, Williamson P
Department of Biochemistry and Molecular Biology, Penn State University, University Park, Pennsylvania 16802, USA.
Adv Exp Med Biol. 1996;406:21-8. doi: 10.1007/978-1-4899-0274-0_3.
Erythrocytes have an asymmetric distribution of phospholipids across the bilayer of their plasma membranes, maintained by an ATP-dependent aminophospholipid translocase, and dissipated by activation of a non-specific lipid flipsite. Loss of asymmetry provokes recognition by the reticuloendothelial system. In vitro, enhanced phagocytosis of erythrocytes with a symmetric bilayer can be inhibited by artificial lipid vesicles made of phosphatidylserine (PS), indicating that macrophages recognize the PS that appears on the erythrocyte surface upon loss of asymmetry. It is becoming increasingly clear that these same fundamental membrane structure/function relationships established in the erythrocyte paradigm also apply to lymphocytes. All evidence suggests that lymphocytes maintain an asymmetric transbilayer distribution of phospholipids in their plasma membranes, maintained by an aminophospholipid translocase. Asymmetry is lost as part of the program of cell death, by down-regulation of the translocase and activation of the non-specific lipid flipsite, exposing PS on the cell surface. That PS exposure has functional consequences is demonstrated by the ability of artificial lipid vesicles containing PS to inhibit enhanced phagocytosis of apoptotic lymphocytes by macrophages. However, other signals besides PS are also involved in recognition of apoptotic lymphocytes. Studies with other inhibitors indicate that macrophages also utilize integrin-mediated and lectin-like recognition systems, although each is restricted to either unactivated or activated macrophages. These results indicate that although many fundamental features of recognition by the reticuloendothelial system may be analogous in erythrocytes and lymphocytes, the signals for recognition of apoptotic lymphocytes ae more complex and involve multiple recognition systems.
红细胞质膜双层中的磷脂分布不对称，这种不对称由一种ATP依赖的氨基磷脂转位酶维持，并通过非特异性脂质翻转位点的激活而消散。不对称性的丧失会引发网状内皮系统的识别。在体外，由磷脂酰丝氨酸（PS）制成的人工脂质囊泡可抑制对具有对称双层的红细胞的吞噬作用增强，这表明巨噬细胞识别不对称性丧失时出现在红细胞表面的PS。越来越清楚的是，在红细胞模式中建立的这些相同的基本膜结构/功能关系也适用于淋巴细胞。所有证据表明，淋巴细胞在其质膜中维持磷脂的不对称跨膜分布，由氨基磷脂转位酶维持。作为细胞死亡程序的一部分，不对称性会丧失，通过转位酶的下调和非特异性脂质翻转位点的激活，使PS暴露在细胞表面。含有PS的人工脂质囊泡能够抑制巨噬细胞对凋亡淋巴细胞吞噬作用增强，这证明了PS暴露具有功能后果。然而，除了PS之外，其他信号也参与凋亡淋巴细胞的识别。使用其他抑制剂的研究表明，巨噬细胞也利用整合素介导的和凝集素样识别系统，尽管每种系统都仅限于未激活或激活的巨噬细胞。这些结果表明，尽管网状内皮系统识别的许多基本特征在红细胞和淋巴细胞中可能类似，但凋亡淋巴细胞识别的信号更为复杂，涉及多个识别系统。
