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人类红细胞C3b/C4b受体(CR1,CD35)的分解代谢:形成囊泡和/或蛋白水解?

Catabolism of the human erythrocyte C3b/C4b receptor (CR1, CD35): vesiculation and/or proteolysis?

作者信息

Dervillez X, Oudin S, Libyh M T, Tabary T, Reveil B, Philbert F, Bougy F, Pluot M, Cohen J H

机构信息

Laboratoire d'Immunologie, CHU Robert Debré, Reims, France.

出版信息

Immunopharmacology. 1997 Dec;38(1-2):129-40. doi: 10.1016/s0162-3109(97)00066-0.

DOI:10.1016/s0162-3109(97)00066-0
PMID:9476124
Abstract

Human erythrocytes (E) react by exocytosis of membrane vesicles to various stresses including the fixation of the membrane attack complex of Complement. E from normal individuals loose a notable proportion of their initial number of surface CR1 molecules during the ageing process. An acquired decrease of CR1 on E also occurs in pathological conditions such as Systemic Lupus Erythematosus or AIDS. The present study investigated whether calcium ionophore A23187 (Ca-ion) induced vesicle formation of human E in vitro is responsible for a preferential loss of CR1 as well as whether CR1 molecules at the surface of Ca-ion treated E or vesicles are: (i) functional, (ii) native or protease degraded, or (iii) more clustered than CR1 on native E. A study of E from 137 normal individuals showed that a one-hour Ca-ion induced vesicle formation preferentially removed one third of E surface CR1. Kinetic experiments suggested that all surface CR1 could be removed from E upon longer incubation times. CR1 molecules on vesicles were still able to inhibit Complement activation, and were found in larger clusters than on native E. These data suggest that a significant part of surface CR1 molecules may be removed from E by vesicle formation during the life of E in normal individuals. This phenomenon could be exacerbated in pathological conditions.

摘要

人类红细胞(E)通过膜泡的胞吐作用对包括补体膜攻击复合物固定在内的各种应激作出反应。正常个体的红细胞在衰老过程中会失去相当比例的初始表面CR1分子数量。在系统性红斑狼疮或艾滋病等病理状况下,红细胞表面的CR1也会出现后天性减少。本研究调查了钙离子载体A23187(Ca-ion)在体外诱导人红细胞形成囊泡是否会导致CR1优先丢失,以及经Ca-ion处理的红细胞或囊泡表面的CR1分子是否:(i)具有功能,(ii)是天然的还是经蛋白酶降解的,或者(iii)比天然红细胞表面的CR1聚集程度更高。对137名正常个体的红细胞研究表明,1小时的Ca-ion诱导囊泡形成优先去除了三分之一的红细胞表面CR1。动力学实验表明,延长孵育时间后,所有表面CR1都可从红细胞中去除。囊泡上的CR1分子仍能抑制补体激活,且发现其比天然红细胞上的CR1聚集程度更高。这些数据表明,在正常个体红细胞的生命周期中,表面CR1分子的很大一部分可能通过囊泡形成从红细胞中被去除。这种现象在病理状况下可能会加剧。

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