Owen J S, Brown D J, Harry D S, McIntyre N, Beaven G H, Isenberg H, Gratzer W B
J Clin Invest. 1985 Dec;76(6):2275-85. doi: 10.1172/JCI112237.
Echinocytes were frequently found in patients with liver disease when their blood was examined in wet films, but rarely detected in dried, stained smears. When normal erythrocytes (discocytes) were incubated with physiologic concentrations of the abnormal high density lipoproteins (HDL) from some jaundiced patients, echinocytosis developed within seconds. Other plasma fractions were not echinocytogenic. There was a close correlation between the number of echinocytes found in vivo and the ability of the corresponding HDL to induce discocyte-echinocyte transformation. On incubation with normal HDL, echinocytes generated in vitro rapidly reverted to a normal shape, and echinocytes from patients showed a similar trend. Echinocytosis occurred without change in membrane cholesterol content, as did its reversal, and was not caused by membrane uptake of lysolecithin or bile acids. Abnormal, echinocytogenic HDL showed saturable binding to approximately 5,000 sites per normal erythrocyte with an association constant of 10(8) M-1. Nonechinocytogenic patient HDL and normal HDL showed only nonsaturable binding. Several minor components of electrophoretically separated erythrocyte membrane proteins bound the abnormal HDL; pretreatment of the cells with trypsin or pronase reduced or eliminated binding. Echinocytosis by abnormal HDL required receptor occupancy, rather than transfer of constituents to or from the membrane, because cells reversibly prefixed in the discoid shape by wheat germ agglutinin, and then exposed to abnormal HDL, did not become echinocytes when the HDL and lectin were successively removed. Binding did not cause dephosphorylation of spectrin. We conclude that the echinocytes of liver disease are generated from discocytes by abnormal HDL, and we infer that the shape change is mediated by cell-surface receptors for abnormal HDL molecules.
棘红细胞在肝病患者的湿片血液检查中经常被发现，但在干燥、染色涂片上很少被检测到。当正常红细胞（双凹圆盘状红细胞）与一些黄疸患者生理浓度的异常高密度脂蛋白（HDL）一起孵育时，几秒钟内就会出现棘红细胞增多现象。其他血浆成分没有诱导棘红细胞形成的作用。体内发现的棘红细胞数量与相应HDL诱导双凹圆盘状红细胞向棘红细胞转化的能力之间存在密切相关性。与正常HDL孵育时，体外产生的棘红细胞会迅速恢复正常形状，来自患者的棘红细胞也表现出类似趋势。棘红细胞增多现象发生时膜胆固醇含量没有变化，其逆转时也是如此，并且不是由溶血卵磷脂或胆汁酸的膜摄取引起的。异常的、能诱导棘红细胞形成的HDL与每个正常红细胞上约5000个位点表现出饱和结合，结合常数为10(8) M-1。不能诱导棘红细胞形成的患者HDL和正常HDL仅表现出非饱和结合。电泳分离的红细胞膜蛋白的几个次要成分与异常HDL结合；用胰蛋白酶或链霉蛋白酶预处理细胞会减少或消除这种结合。异常HDL引起的棘红细胞增多需要受体被占据，而不是成分向膜内或从膜内转移，因为用麦胚凝集素可逆地固定在双凹圆盘状形状的细胞，然后暴露于异常HDL，当HDL和凝集素相继去除时不会变成棘红细胞。结合不会导致血影蛋白去磷酸化。我们得出结论，肝病患者的棘红细胞是由异常HDL从双凹圆盘状红细胞产生的，并且我们推断这种形状变化是由异常HDL分子的细胞表面受体介导的。
