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


CONCLUSIONS
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.
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Anders
A
Etzerodt
Mads
M
Kjolby
Marianne Jensby
MJ
Nielsen
Maciej
M
Maniecki
Pia
P
Svendsen
Søren Kragh
SK
Moestrup
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D015870:Gene Expression; D018390:Gene Targeting; D005838:Genotype; D006242:Haptoglobins / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D046912:Multiprotein Complexes / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D020349:Surface Plasmon Resonance; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D046912:Multiprotein Complexes; D011956:Receptors, Cell Surface