ERYTHROCYTE SENESCENCE

红细胞衰老的机制是一个尚未解决的问题。 甚至 尽管对基因决定的溶血性贫血的研究 证明了各种缺陷，可以缩短红细胞寿命 跨度，没有明确的答案已经出现的正常机制， 确定红细胞存活。 红细胞衰老的检测 由于分离老化细胞的困难而受到阻碍。 各种 已经使用了一些技术来获得这些衰老的红细胞 但大多数都不令人满意。 该提案描述了一种新的程序， 从家兔中分离衰老红细胞。 与此 技术，兔红细胞用生物素共价标记， 与N-羟基琥珀酰亚胺生物素反应。 已显示结合的生物素 为了在输注衍生化细胞时不影响红细胞存活 进入兔子。 在输注后的不同时间， 红细胞可以通过亲和素亲和性选择性地回收 层析 通过该程序，常规分离红细胞 在预期死亡后的5到10天内 这些衰老的红细胞 已经发现具有正常水平的腺苷5' -三磷酸。 的 目前的建议将研究这些衰老的额外特征， 红细胞包括糖酵解和 磷酸己糖途径，腺嘌呤核苷酸相关酶 代谢，细胞抗氧化防御的状态， 细胞表面的抗体和骨架/膜的完整性 复杂. 对这些参数的仔细检查应该会导致一个更好的 了解控制正常衰老的因素， 红细胞

The mechanism of erythrocyte senescence remains an unsolved problem. Even though the study of genetically determined hemolytic anemias has demonstrated a variety of defects which can shorten the erythrocyte life span, no clear cut answer has emerged as to the normal mechanisms which determine erythrocyte survival. The examination of erythrocyte senescence has been hindered by the difficulty of isolating aged cells. A variety of techniques have been utilized for obtaining these senescent erythrocytes but most are not satisfactory. This proposal describes a new procedure for the isolation of senescent erythrocytes from the rabbit. With this technique, rabbit erythrocytes are covalently labeled with biotin by reaction with N-hydroxysuccinimido biotin. The bound biotin has been shown to not affect erythrocyte survival when the derivatized cells are infused into the rabbit. At various times after infusion, the biotinylated erythrocytes can be selectively recovered by avidin affinity chromatography. With this procedure, erythrocytes are routinely isolated within 5 to 10 days of their expected death. These senescent erythrocytes have been found to have normal levels of adenosine 5' - triphosphate. The present proposal will examine additional characteristics of these senescent erythrocytes including the integrity of the glycolytic and hexosemonophosphate pathways, the enzymes related to adenine nucleotide metabolism, the state of the cellular anti-oxidant defenses, the level of antibodies on the cell surface and the integrity of the skeleton/membrane complex. A careful examination of these parameters should lead to a better understanding of factors which control the normal senescence of erythrocytes.