Søren Kragh Moestrup

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

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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 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 non-complexed mouse Hb has a higher CD163 affinity than human Hb has. Moreover, CD163-mediated uptake in mice seems only to account for a part of the Hb clearance. The new data further underscores that the Hp system in man seems to have a broader and more sophisticated role. This has major implications in translation of data on Hb metabolism from mouse to man.
Original languageEnglish
JournalAntioxidants & Redox Signaling
Volume18
Issue17
Pages (from-to)2254-2263
ISSN1523-0864
DOIs
Publication statusPublished - 2013

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