Jensen L E, Hiney M P, Shields D C, Uhlar C M, Lindsay A J, Whitehead A S
Department of Genetics and Biotechnology Institute, Trinity College, Dublin, Ireland.
J Immunol. 1997 Jan 1;158(1):384-92.
Inflammation induces dramatic changes in the biosynthetic profile of the liver, leading to increased serum concentrations of positive acute phase (AP) proteins and decreased concentrations of negative AP proteins. Serum amyloid A (SAA) and the pentraxins C-reactive protein (CRP) and serum amyloid P component (SAP) are major AP proteins: their serum levels can rise by 1000-fold, indicating that they play a critical role in defense and/or the restoration of homeostasis. We have cloned SAA and a SAP-like pentraxin from salmonid fish species. The salmonid SAA shares approximately 70% amino acid identity with mammalian AP SAA. When salmonids are challenged with an AP stimulus, i.e., Aeromonas salmonicida, SAA responds dramatically as a major AP reactant. The salmonid pentraxin shows approximately 40% amino acid identity to both mammalian SAP and CRP. Evolutionary analysis suggests the presence of only a single such protein in teleosts and lower animal species. Surprisingly, the salmonid pentraxin behaves as a negative AP reactant, reminiscent of the SAP-like Syrian hamster female protein, in that hepatic mRNA concentrations decline to 50% of prestimulus levels. This study reinforces the hypothesis that SAA induction is an essential and universal feature of the vertebrate AP response and that it represents part of an ancient host defense system. Conversely, the species-dependent heterogeneity of pentraxin expression during the vertebrate AP response supports the possibility that its most important ancestral (and perhaps present) function is not related to its AP behavior.
炎症会引起肝脏生物合成谱的显著变化,导致血清中阳性急性期(AP)蛋白浓度升高,阴性AP蛋白浓度降低。血清淀粉样蛋白A(SAA)、五聚体蛋白C反应蛋白(CRP)和血清淀粉样蛋白P成分(SAP)是主要的AP蛋白:它们的血清水平可升高1000倍,表明它们在防御和/或内环境稳态恢复中起关键作用。我们已从鲑科鱼类中克隆出SAA和一种类似SAP的五聚体蛋白。鲑科SAA与哺乳动物AP SAA的氨基酸同一性约为70%。当鲑科鱼类受到AP刺激,即杀鲑气单胞菌刺激时,SAA作为主要的AP反应物会产生显著反应。鲑科五聚体蛋白与哺乳动物SAP和CRP的氨基酸同一性约为40%。进化分析表明硬骨鱼和低等动物物种中仅存在一种此类蛋白。令人惊讶的是,鲑科五聚体蛋白表现为阴性AP反应物,这让人想起叙利亚仓鼠雌性类似SAP的蛋白,即肝脏mRNA浓度降至刺激前水平的50%。这项研究强化了以下假说:SAA诱导是脊椎动物AP反应的一个基本且普遍的特征,并且它代表了一种古老的宿主防御系统的一部分。相反,脊椎动物AP反应期间五聚体蛋白表达的物种依赖性异质性支持了这样一种可能性,即其最重要的祖先(也许还有目前)功能与其AP行为无关。