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小鼠急性接触乙醇后补体介导的免疫清除的选择性、长期改变。

Selective, prolonged alteration of complement-mediated immune clearance after acute exposure of mice to ethanol.

作者信息

Messner R P, Meryhew N L, DeMaster E G

机构信息

Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.

出版信息

Clin Immunol Immunopathol. 1994 Jan;70(1):73-80. doi: 10.1006/clin.1994.1013.

DOI:10.1006/clin.1994.1013
PMID:8261672
Abstract

A selective and prolonged alteration in complement-mediated immune clearance was found in mice given a single intraperitoneal injection of ethanol. Rate constants for the separate components of complement- and IgG Fc gamma-mediated clearance were determined using a branched series, first-order reaction sequence model and measurements of the disappearance of radiolabeled IgG-opsonized murine erythrocytes from the circulation of BALB/c mice. The rate constant governing immune clearance mediated by IgG Fc gamma receptors (k3) decreased to 16% of control at 1 hr after ethanol injection but returned to normal in 72 hr. A > 50% decrease in complement-mediated clearance occurred, with a nadir of complement-mediated sequestration (k1) and complement-dependent phagocytosis (k4) at 1 hr (P < 0.001). In this case, however, k1 and k4 rate constant values did not return to control levels until 6 weeks after the injection of ethanol. The rate constant governing C3b deactivation and release of deactivated, sensitized cells back to the circulation before they undergo phagocytosis (k2) was initially normal, but decreased in Week 6 and remained low to the end of the observation period at 22 weeks (P < 0.0001). These changes resulted in a major reduction in overall complement-mediated immune clearance up to 4 weeks after the ethanol injection. The change to normal rates for sequestration and phagocytosis coupled with decreased deactivation and release at 6 weeks postinjection resulted in a small increase in overall complement-mediated clearance that persisted through Week 22.

摘要

给小鼠腹腔注射一次乙醇后,发现其补体介导的免疫清除存在选择性且持续时间较长的改变。使用分支串联一级反应序列模型,并通过测量放射性标记的IgG调理的小鼠红细胞在BALB/c小鼠循环中的消失情况,确定了补体和IgG Fcγ介导的清除各组分的速率常数。乙醇注射后1小时,由IgG Fcγ受体介导的免疫清除速率常数(k3)降至对照值的16%,但在72小时后恢复正常。补体介导的清除率下降超过50%,补体介导的隔离(k1)和补体依赖性吞噬作用(k4)在1小时时降至最低点(P<0.001)。然而,在这种情况下,k1和k4速率常数直到乙醇注射后6周才恢复到对照水平。在致敏细胞被吞噬之前,控制C3b失活以及失活的致敏细胞释放回循环的速率常数(k2)最初正常,但在第6周下降,并在观察期结束时的22周一直保持较低水平(P<0.0001)。这些变化导致乙醇注射后长达4周的时间里,补体介导的总体免疫清除大幅降低。注射后6周时,隔离和吞噬作用的速率恢复正常,同时失活和释放减少,导致补体介导的总体清除率略有增加,并持续到第22周。

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