Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Antioxid Redox Signal. 2013 Jun 10;18(17):2254-63. doi: 10.1089/ars.2012.4605. Epub 2012 Aug 29.
In humans, plasma haptoglobin (Hp) and the macrophage receptor CD163 promote a fast scavenging of hemoglobin (Hb). In the present study, we have compared the mouse and human CD163-mediated binding and uptake of Hb and HpHb complex in vitro and characterized the CD163-mediated plasma clearance of Hb in CD163 gene knockout mice and controls.
Contrary to human Hp, mouse Hp did not promote high-affinity binding to CD163. This difference between mouse and man was evident both by analysis of the binding of purified proteins and by ligand uptake studies in CD163-transfected cells. Plasma clearance studies in mice showed a fast clearance (half-life few minutes) of fluorescently labeled mouse Hb with the highest uptake in the kidney and liver. HPLC analysis of serum showed that the clearance curve exhibited a two-phase decay with a faster clearance of Hb than plasma-formed HpHb. In CD163-deficient mice, the overall clearance of Hb was slightly slower and followed a one-phase decay.
In conclusion, mouse Hp does not promote high-affinity binding of mouse Hb to CD163, and noncomplexed mouse Hb has a higher CD163 affinity than human Hb has. Moreover, CD163-mediated uptake in mice seems to only account for a part of the Hb clearance. The new data further underscore the fact that the Hp system in man seems to have a broader and more sophisticated role. This has major implications in the translation of data on Hb metabolism from mouse to man.
在人类中，血浆触珠蛋白（Hp）和巨噬细胞受体 CD163 促进血红蛋白（Hb）的快速清除。在本研究中，我们比较了小鼠和人类 CD163 介导的 Hb 和 HpHb 复合物在体外的结合和摄取，并在 CD163 基因敲除小鼠和对照小鼠中表征了 CD163 介导的 Hb 血浆清除。
与人类 Hp 相反，小鼠 Hp 不能促进与 CD163 的高亲和力结合。这种小鼠与人之间的差异在通过分析纯化蛋白的结合和通过转染 CD163 的细胞中的配体摄取研究来证实。在小鼠中的血浆清除研究显示，荧光标记的小鼠 Hb 具有快速清除（半衰期几分钟），在肾脏和肝脏中的摄取量最高。血清的 HPLC 分析表明，清除曲线呈两相衰减，Hb 的清除速度快于血浆形成的 HpHb。在 CD163 缺陷型小鼠中，整体 Hb 清除速度稍慢，呈单相衰减。
总之，小鼠 Hp 不能促进小鼠 Hb 与 CD163 的高亲和力结合，并且未复合的小鼠 Hb 对 CD163 的亲和力高于人类 Hb。此外，小鼠中的 CD163 介导摄取似乎仅占 Hb 清除的一部分。新数据进一步强调了这样一个事实，即人类 Hp 系统似乎具有更广泛和更复杂的作用。这对将 Hb 代谢数据从小鼠转化为人类具有重要意义。
