HUMAN INTER-ALPHA-INHIBITOR FAMILY IN INFLAMMATION - SIMULTANEOUS SYNTHESIS OF POSITIVE AND NEGATIVE ACUTE-PHASE PROTEINS
HUMAN INTER-ALPHA-INHIBITOR FAMILY IN INFLAMMATION - SIMULTANEOUS SYNTHESIS OF POSITIVE AND NEGATIVE ACUTE-PHASE PROTEINS
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DOI：
10.1042/bj2920485
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发表时间：
1993-06-01
影响因子：
4.1
通讯作者：
SALIER, JP
中科院分区：
文献类型：
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作者：
DAVEAU, M;ROUET, P;SALIER, JP
IalphaI家族包括四种血浆蛋白，即游离Bikunin、IalphaI、前AlphaI和IalphaI。最后三种蛋白质中的每一种都是一个Bikunin链的不同组装，其中一个或多个唯一的重(H)链被命名为H1、H2和H3。三个H链和bikunin链由四个不同的mRNAs编码。这些分子和链以及相应的mRNAs在一系列患有或不患有轻度或严重急性感染的患者的血清和肝脏活检中进行了量化。在血清中观察到的特定分子或链的减少或增加与相应的肝脏mRNA的类似变化是一致的。在急性炎症中，H2和bikunin链下调，相关分子IalphaI，IalphaLI)表现为负急性时相蛋白，而H3链上调，相应的PalphaI分子为阳性急性时相蛋白。此外，PalphaI显示的M(R)比平时高；这可能是由于配体结合所致。H1基因似乎不受炎症状态的影响。体内观察到的RNA水平的定量变化在体外证实了人肝癌Hep3B细胞系在急性时相介质IL-1和/或-6诱导之前或之后的定量变化。这些结果在人类中提供了第一个由进化相关基因编码的阳性和阴性急性时相蛋白的例子。
The inter-alpha-inhibitor (IalphaI) family encompasses four plasma proteins, namely free bikunin as well as IalphaI, pre-alpha-inhibitor (PalphaI) and inter-alpha-like inhibitor (IalphaI). Each of the last three proteins is a distinct assembly of one bikunin chain with one or more unique heavy (H) chains designated H1, H2 and H3. The three H chains and the bikunin chain are encoded by four distinct mRNAs. These molecules and chains, as well as the corresponding mRNAs, were quantified in sera and liver biopsies from a series of patients with or without mild or severe acute infection. The decrease or increase observed for a given molecule or chain in the serum was in agreement with a similar change in the corresponding liver mRNA. In acute inflammation the H2 and bikunin chains are down-regulated and the relevant molecules IalphaI, IalphaLI) behave as negative acute-phase proteins, whereas the H3 chain is up-regulated and the corresponding PalphaI molecule is a positive acute-phase protein. Also, PalphaI displays a higher-than-usual M(r); this is probably due to ligand binding. The H1 gene does not seem to be affected by the inflammatory condition. The quantitative changes in RNA levels seen in vivo were confirmed in vitro in the human hepatoma Hep3B cell line prior to or after induction with the acute-phase mediators interleukin-1 and/or -6. These results provide the first example in humans of positive and negative acute-phase proteins that are encoded by evolutionary related genes.