Submitted May 15, 2006
Accepted May 30, 2006
Haptoglobin-related protein is a high-affinity
hemoglobin-binding plasma protein
Marianne Jensby Nielsen, Steen Vang Petersen, Christian Jacobsen, Claus Oxvig, David Rees, Holger Jon Moller, and Soren Kragh Moestrup*
Department of Medical Biochemistry, University of Aarhus
Department of Molecular Biology, University of Aarhus
Department of Paediatric Haematology, King's College School of Medicine, King's College Hospital
Department of Clinical Biochemistry, Aarhus University Hospital
* Corresponding author; email: skm{at}biokemi.au.dk.
Haptoglobin-related protein (Hpr) is a primate-specific
plasma protein associated with apolipoprotein L-I (apoL
I)-containing high density lipoprotein (HDL) particles
shown to be a part of the innate immune defense. Despite
the assumption hitherto that Hpr does not bind to
hemoglobin, the present study revealed that recombinant
Hpr binds hemoglobin as efficiently as haptoglobin (Hp).
However, in contrast to Hp, Hpr did not promote any high-
affinity binding to the scavenger receptor CD163.
Binding of hemoglobin to circulating native Hpr
incorporated into the HDL fraction was indicated by
hemoglobin-affinity precipitation of plasma Hpr together
with apoL I. In conclusion, plasma has two high-affinity
haemoglobin-binding haptoglobins instead of one, but
only Hp hemoglobin complexes are efficiently recognized
by CD163. Circulating Hpr-bound hemoglobin should
therefore be taken into consideration when measuring
'free' plasma hemoglobin. Furthermore, Hpr-bound
hemoglobin might contribute to the biological activity
of the circulating apoL-I/Hpr-containing HDL particles.
