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.
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 humanCD163-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.
Authors: Kristin M Whitworth; Raymond R R Rowland; Catherine L Ewen; Benjamin R Trible; Maureen A Kerrigan; Ada G Cino-Ozuna; Melissa S Samuel; Jonathan E Lightner; David G McLaren; Alan J Mileham; Kevin D Wells; Randall S Prather Journal: Nat Biotechnol Date: 2015-12-07 Impact factor: 54.908
Authors: Jan A Graw; Binglan Yu; Emanuele Rezoagli; H Shaw Warren; Emmanuel S Buys; Donald B Bloch; Warren M Zapol Journal: Am J Physiol Heart Circ Physiol Date: 2017-03-17 Impact factor: 4.733
Authors: Miriam Lipiski; Jeremy W Deuel; Jin Hyen Baek; Wolfgang R Engelsberger; Paul W Buehler; Dominik J Schaer Journal: Antioxid Redox Signal Date: 2013-03-28 Impact factor: 8.401
Authors: Patricia A Shi; Erika Choi; Narendranath R Chintagari; Julia Nguyen; Xinhua Guo; Karina Yazdanbakhsh; Narla Mohandas; Abdu I Alayash; Elizabeth A Manci; John D Belcher; Gregory M Vercellotti Journal: Br J Haematol Date: 2016-08-10 Impact factor: 6.998