Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells
Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells
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DOI：
10.1039/c3mt00347g
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发表时间：
2014-01-01
期刊：
影响因子：
3.4
通讯作者：
Pretorius, Etheresia
中科院分区：
文献类型：
--
作者：
Kell, Douglas B.;Pretorius, Etheresia
“血清铁蛋白”是一个悖论，因为铁储存蛋白铁蛋白不是在血清中合成的，但在那里被发现。血清铁蛋白也是一个众所周知的炎症标志物，但目前尚不清楚血清铁蛋白是否反映或引起炎症，或是否参与炎症周期。我们认为，血清铁蛋白来自受损细胞，因此是细胞损伤的标志物。血清铁蛋白中的蛋白质被认为是良性的，但它已经失去了（即倾倒）大部分正常的铁补充，当脱配体时是剧毒的。血清铁蛋白水平与疾病和体内铁储备相关的事实，因此可以从简单的化学动力学基础上进行预测。血清铁蛋白水平也与其他表型读数如红细胞形态相关。总的来说，这种系统方法用于解释血清铁蛋白的许多明显的矛盾，包括（i）为什么它与细胞损伤的生物标志物相关，（ii）为什么它与羟基自由基形成（和氧化应激）的生物标志物相关，以及（iii）为什么它与许多疾病的存在和/或严重程度相关。这就引出了人们如何利用血清铁蛋白水平主要代表细胞应激和损伤的结果这一认识的推论的建议。
"Serum ferritin" presents a paradox, as the iron storage protein ferritin is not synthesised in serum yet is to be found there. Serum ferritin is also a well known inflammatory marker, but it is unclear whether serum ferritin reflects or causes inflammation, or whether it is involved in an inflammatory cycle. We argue here that serum ferritin arises from damaged cells, and is thus a marker of cellular damage. The protein in serum ferritin is considered benign, but it has lost (i.e. dumped) most of its normal complement of iron which when unliganded is highly toxic. The facts that serum ferritin levels can correlate with both disease and with body iron stores are thus expected on simple chemical kinetic grounds. Serum ferritin levels also correlate with other phenotypic readouts such as erythrocyte morphology. Overall, this systems approach serves to explain a number of apparent paradoxes of serum ferritin, including (i) why it correlates with biomarkers of cell damage, (ii) why it correlates with biomarkers of hydroxyl radical formation (and oxidative stress) and (iii) therefore why it correlates with the presence and/or severity of numerous diseases. This leads to suggestions for how one might exploit the corollaries of the recognition that serum ferritin levels mainly represent a consequence of cell stress and damage.