Hu S I, Macintyre S S, Schultz D, Kushner I, Samols D
Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106.
J Biol Chem. 1988 Jan 25;263(3):1500-4.
C-reactive protein (CRP) is a major acute phase protein in humans and rabbits. Its synthesis by the liver varies over a 1000-fold range depending on the presence and severity of inflammatory stimuli. In previous studies of synthesis and secretion of rabbit CRP, we showed that secretion becomes more efficient over the course of the acute phase response as CRP synthesis rates increase (Macintyre, S.S., Kushner, I., and Samols, D. (1985) J. Biol. Chem. 260, 4169-4173). The current studies were undertaken to help distinguish between two alternative explanations for this finding: 1) that secretion efficiency may simply be a property of the rate of synthesis and intracellular concentration of CRP or 2) that secretion may be regulated by separate intracellular mechanisms. A fusion gene containing the mouse metallothionein I promoter linked to the protein coding region of the rabbit CRP gene was introduced into the human hepatoma cell line, NPLC, and the nonliver cell line, HeLa. In this system a graded response of the mouse metallothionein I promoter following exposure to increasing zinc concentrations results in increasing CRP synthesis. Unlike hepatocytes from rabbits undergoing the acute phase response, we found that rabbit CRP was secreted by these transfected cell lines with a very high degree of efficiency which was independent of the rate of CRP synthesis. This finding implies that normal rabbit hepatocytes retard the secretion of CRP and that this inhibition is diminished as the acute phase response progresses. It further indicates that the relationship between changes in synthetic rate and efficiency of secretion of rabbit CRP is not a causal one and that synthesis and secretion of CRP by rabbit hepatocytes are regulated by independent intracellular mechanisms during the acute phase response.
C反应蛋白（CRP）是人和兔子体内一种主要的急性期蛋白。肝脏对其合成量会因炎症刺激的存在与否及严重程度而在1000倍的范围内变化。在之前关于兔子CRP合成与分泌的研究中，我们发现随着CRP合成速率在急性期反应过程中增加，分泌变得更高效（麦金太尔，S.S.，库什纳，I.，和萨莫尔斯，D.（1985年）《生物化学杂志》260卷，4169 - 4173页）。进行当前这些研究是为了帮助区分对这一发现的两种不同解释：1）分泌效率可能仅仅是CRP合成速率和细胞内浓度的一种特性，或者2）分泌可能受独立的细胞内机制调控。一个包含与兔子CRP基因蛋白质编码区相连的小鼠金属硫蛋白I启动子的融合基因被导入人肝癌细胞系NPLC和非肝细胞系HeLa。在这个系统中，暴露于不断增加的锌浓度后，小鼠金属硫蛋白I启动子的分级反应会导致CRP合成增加。与处于急性期反应的兔子肝细胞不同，我们发现这些转染的细胞系能非常高效地分泌兔子CRP，且这种效率与CRP合成速率无关。这一发现意味着正常兔子肝细胞会阻碍CRP的分泌，并且随着急性期反应的进展这种抑制作用会减弱。它还进一步表明兔子CRP合成速率变化与分泌效率之间的关系并非因果关系，并且在急性期反应期间兔子肝细胞中CRP的合成和分泌受独立的细胞内机制调控。
