Singer J A, Jennings L K, Jackson C W, Dockter M E, Morrison M, Walker W S
Proc Natl Acad Sci U S A. 1986 Aug;83(15):5498-501. doi: 10.1073/pnas.83.15.5498.
We tested the hypothesis that the accumulation of bound autologous antibody on a "senescent epitope" identifies aged erythrocytes for phagocytic removal by macrophages. Erythrocytes were collected from mice maintained on a hypertransfusion protocol designed to yield cells of defined age. The mouse erythrocytes were assayed for the presence of bound antibody by measuring their susceptibility to ingestion by macrophages from mouse peritoneal exudates and by flow cytofluorometry. Both assays disclosed that only the oldest mouse erythrocytes bore detectable levels of antibody. Flow cytofluorometric analysis revealed that the frequency distribution of IgG isotypes bound to the cells reflected their levels in normal serum. Finally, treatment with trypsin abolished the ability of the macrophages to ingest erythrocytes aged in vivo. These findings support the hypothesis that antibody mediates the clearance of senescent mouse erythrocytes from the circulation and demonstrate that the presence of a trypsin-sensitive recognition structure on macrophages is an essential requirement in this homeostatic process.
结合在“衰老表位”上的自体抗体的积累可识别衰老红细胞,以便巨噬细胞进行吞噬清除。红细胞取自按照超输血方案饲养的小鼠,该方案旨在产生特定年龄的细胞。通过测量小鼠腹膜渗出液中的巨噬细胞对其摄取的敏感性以及流式细胞荧光术,检测小鼠红细胞上结合抗体的存在情况。两种检测方法均显示,只有最老的小鼠红细胞带有可检测水平的抗体。流式细胞荧光分析表明,与细胞结合的IgG同种型的频率分布反映了它们在正常血清中的水平。最后,用胰蛋白酶处理消除了巨噬细胞摄取体内老化红细胞的能力。这些发现支持了抗体介导衰老小鼠红细胞从循环中清除的假说,并证明巨噬细胞上存在对胰蛋白酶敏感的识别结构是这一稳态过程的基本要求。