Messner R P, Meryhew N L, DeMaster E G
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
J Lab Clin Med. 1993 Nov;122(5):506-17.
Rate constants (k1 through k4) describing complement-mediated and Fc gamma receptor-mediated components of immune clearance were serially determined in BALB/c mice fed ethanol, 10%, in drinking water, for 24 weeks. A branched series, first order reaction sequence model of immune clearance was used to obtain the rate constants from measurements of the clearance of radiolabeled immunoglobulin G-opsonized, murine erythrocytes. A > 50% decrease in complement-mediated clearance occurred, with a nadir of complement-mediated sequestration (k1) and complement-dependent phagocytosis (k4) at 2 weeks (p < 0.003). Mean k1 and k4 rate constant values returned to control levels by week 6, and k1 increased to elevated values in weeks 10 through 20 (p < 0.05). The rate constant governing C3b deactivation and return of deactivated, sensitized cells back to the circulation (k2) was initially normal but decreased in weeks 6 through 24 (p < 0.05). Neither immunoglobulin G Fc gamma receptor-mediated clearance nor the survival of nonsensitized cells were decreased by ethanol. Mice fed ethanol had a mean blood alcohol level of 14.9 +/- 7.2 mmol/L, and their mean weight and serum complement levels did not differ from untreated controls. Complement-dependent sequestration and phagocytosis did not decrease significantly when rechallenged with 10% ethanol, but the decrease in k2 and increase in k1 did occur on rechallenge. Thus, chronic ethanol ingestion in mice is associated with an initial decrease followed by a small rebound increase in complement-mediated clearance of opsonized cells. Fc gamma receptor-mediated clearance is not decreased, and only the rebound increase in complement-mediated clearance is observed on rechallenge. This model provides a unique opportunity to study selective in vivo effects of ethanol on an important function of the immune system as well as to explore the mechanisms of ethanol tolerance in mice.
在饮用含10%乙醇的饮用水24周的BALB/c小鼠中，连续测定了描述补体介导和Fcγ受体介导的免疫清除成分的速率常数（k1至k4）。使用免疫清除的分支串联一级反应序列模型，从放射性标记的免疫球蛋白G调理的小鼠红细胞清除率的测量中获得速率常数。补体介导的清除率下降超过50%，在第2周时补体介导的隔离（k1）和补体依赖性吞噬作用（k4）达到最低点（p<0.003）。平均k1和k4速率常数在第6周时恢复到对照水平，在第10周至20周时k1升高至较高值（p<0.05）。控制C3b失活以及失活的致敏细胞返回循环的速率常数（k2）最初正常，但在第6周至24周时下降（p<0.05）。乙醇并未降低免疫球蛋白G Fcγ受体介导的清除率或未致敏细胞的存活率。喂食乙醇的小鼠平均血液酒精水平为14.9±7.2 mmol/L，其平均体重和血清补体水平与未处理的对照组无差异。再次用10%乙醇刺激时，补体依赖性隔离和吞噬作用没有显著降低，但再次刺激时k2下降和k1升高确实发生了。因此，小鼠长期摄入乙醇与补体介导的调理细胞清除率最初下降随后小幅反弹增加有关。Fcγ受体介导的清除率没有降低，再次刺激时仅观察到补体介导的清除率的反弹增加。该模型为研究乙醇对免疫系统重要功能的选择性体内效应以及探索小鼠乙醇耐受性机制提供了独特的机会。
