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. 2013 Jun 10;18(17):2254-63.
doi: 10.1089/ars.2012.4605. Epub 2012 Aug 29.

Plasma clearance of hemoglobin and haptoglobin in mice and effect of CD163 gene targeting disruption

Anders Etzerodt  1 , Mads Kjolby, Marianne Jensby Nielsen, Maciej Maniecki, Pia Svendsen, Søren Kragh Moestrup
Affiliations

Plasma clearance of hemoglobin and haptoglobin in mice and effect of CD163 gene targeting disruption

Anders Etzerodt et al. Antioxid Redox Signal. .

Abstract

Aim: 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.

Results: 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.

Innovation and conclusion: 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.

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