Scientific Publications by FDA Staff
Blood 2006 Jan 1;107(1):373-80
CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin.
Schaer DJ, Schaer CA, Buehler PW, Boykins RA, Schoedon G, Alayash AI, Schaffner A
Schaer DJ, Univ Zurich Hosp, Med Clin B, Res Unit, CH-8091 Zurich, Switzerland Univ Zurich Hosp, Med Clin B, Res Unit, CH-8091 Zurich, Switzerland US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20014 USA US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20014 USA
CD163 mediates the internalization of hemoglobin-haptoglobin (Hb-Hp) complexes by macrophages. As Hp binding capacity is exhausted during severe hemolysis, an Hp-independent Hb-clearance pathway is presumed to exist. We demonstrate that Hb interacts efficiently with CD163 in the absence of Hp. Hb is not only internalized into an endosomal compartment by CD163, as a result of active receptor dependent endocytosis; it also inhibits the uptake of Hb-Hp complexes, suggesting a common receptor binding site. Free Hb further induces heme oxygenase mRNA expression in CD163-positive cells, but not in CD163-negative cells. Additional evidence for Hp-independent Hb-CD163 interaction is provided by the demonstration that CD163 mediates uptake of alpha-alpha-DBBF cross-linked Hb, a chemically modified Hb, which forms minimal Hp-complexes. Moreover, certain modifications to Hb, such as polymerization or the addition of specific functional groups (3 lysyl residues) to the beta-Cys93, can either reduce or enhance this pathway of uptake. In human macrophages, Hp-complex formation critically enhances Hb uptake at low (1 microg/mL) but not at high ( >100 microg/mL) ligand concentrations, lending support for a concentration-dependent biphasic model of macrophage Hb-clearance. These results identify CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes following Hp depletion.
|Category: Journal Article, Peer|
|PubMed ID: #16189277|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|