Identification of the haemoglobin scavenger receptor

  title={Identification of the haemoglobin scavenger receptor},
  author={Mette Svart Kristiansen and Jonas Heilskov Graversen and Christian Jacobsen and Ole Sonne and Hans J{\"u}rgen Hoffman and S. K. Alex Law and S{\`u}ren K. Moestrup},
Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders. Haemoglobin released into plasma is captured by the acute phase protein haptoglobin, which is depleted from plasma during elevated haemolysis. Here we report the identification of the acute phase-regulated and signal-inducing macrophage protein, CD163, as a receptor that… 

Haemoglobin scavenger receptor: function in relation to disease.

Besides the observation that the haemoglobin scavenger receptor provides a promising target for new treatment possibilities, it offers a novel view on the aetiology of diverse physiological as well as pathophysiological processes.

CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma.

Structure of the haptoglobin–haemoglobin complex

This structure reveals that haptoglobin molecules dimerize through an unexpected β-strand swap between two complement control protein (CCP) domains, defining a new fusion CCP domain structure.

Gating the radical hemoglobin to macrophages: the anti-inflammatory role of CD163, a scavenger receptor.

An overview and novel insights into the role of CD163 in Hb redox inactivation and clearance are provided and the nature of chemical modifications introduced onto the Hb molecule and/or oxidative changes induced in the protein appear to influence the extent ofCD163 interaction and cellular uptake.

Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma.

SHbSR is an abundant plasma protein potentially valuable in monitoring patients with infections and myelomonocytic leukemia and there are strong indications that HbSR serves an anti-inflammatory function.

Receptor targeting of hemoglobin mediated by the haptoglobins: roles beyond heme scavenging.

Variant human homologous hemoglobin-binding proteins that collectively may be designated the haptoglobins have diverted from the hapticoglobin gene, contributing to different biologic events that go beyond simple removal from plasma of the toxic hemoglobin.

Association between the Haptoglobin and Heme Oxygenase 1 Genetic Profiles and Soluble CD163 in Susceptibility to and Severity of Human Malaria

Increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria, which could support the development of targeted therapies and aid in reducing the severity of malaria.

Enhanced expression of haemoglobin scavenger receptor in accumulated macrophages of culprit lesions in acute coronary syndromes.

A positive association among intraplaque haemorrhage, enhanced expression of Hb scavenger receptor, and lipid peroxidation in human unstable plaques is suggested.

CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobin.

It is demonstrated that Hb interacts efficiently with CD163 in the absence of Hp, identifying CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes after Hp depletion.

Soluble CD163

  • H. Møller
  • Biology, Medicine
    Scandinavian journal of clinical and laboratory investigation
  • 2012
It is now evident that sCD163 is very useful as a biomarker of macrophages activation in various inflammatory diseases, such as macrophage activation syndrome, sepsis, and liver disease, and is a general risk marker of comorbidity and mortality in several chronic inflammatory disease states.



Recognition of oxidatively damaged erythrocytes by a macrophage receptor with specificity for oxidized low density lipoprotein.

Oxidation of plasma membranes results in the formation of lipid-protein conjugate(s) closely related to some of the conjugates found in oxidized LDL, making the oxidized erythrocyte a ligand for the macrophage scavenger receptors, apparently at a site distinct from that responsible for the binding of acetylated LDL.

Human CD14 mediates recognition and phagocytosis of apoptotic cells

Results indicate that clearance of apoptotic cells is mediated by a receptor whose interactions with ‘non-self’ components (LPS) and ‘self” components (apoptotic cells) produce distinct macrophage responses.

The Class B Scavenger Receptors SR-BI and CD36 Are Receptors for Anionic Phospholipids (*)

Using both direct binding and ligand competition assays in transfected cells, it is found that two class B scavenger receptors, SR-BI and CD36, can tightly bind PS and phosphatidylinositol (PI)-containing liposomes.

Regulation of CD163 on human macrophages: cross‐linking of CD163 induces signaling and activation

A function for the SRCR‐superfamily receptor CD163 in the regulation of inflammatory processes by macrophages is suggested, as well as aspects of the tissue distribution, theregulation of expression, and signal transduction after cross‐linking of this receptor at the cell surface of macrophage.

Identification of the integral membrane protein RM3/1 on human monocytes as a glucocorticoid-inducible member of the scavenger receptor cysteine-rich family (CD163).

It is shown for the first time that CD163 is significantly up-regulated by glucocorticoids, suggesting that it might play an important role in inflammatory processes.

Characterization of an Epithelial ∼460-kDa Protein That Facilitates Endocytosis of Intrinsic Factor-Vitamin B12 and Binds Receptor-associated Protein*

The epithelial IF-B12-binding receptor is identified as a ∼460-kDa RAP-binding protein facilitating endocytosis and targeting of vitamin B12 to lysosomes.

beta2-glycoprotein-I (apolipoprotein H) and beta2-glycoprotein-I-phospholipid complex harbor a recognition site for the endocytic receptor megalin.

The data provide molecular evidence for the suggested function of beta2-glycoprotein-I as a linking molecule mediating cellular recognition of phosphatidylserine-exposing particles in patients with renal tubule failure.

Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro‐ and antiinflammatory stimuli

The results demonstrate that CD163 expression in monocytes/macrophages is regulated by proinflammatory and antiinflammatory mediators, implying a functional role of CD163 in the antiinflammatory response of monocytes.

Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein.

The epithelial IF-B12-binding receptor is identified as a approximately 460-kDa RAP-binding protein facilitating endocytosis of renal epithelial tissue.