CD163: a regulated hemoglobin scavenger receptor with a role in the anti‐inflammatory response

  title={CD163: a regulated hemoglobin scavenger receptor with a role in the anti‐inflammatory response},
  author={S{\o}ren Kragh Moestrup and Holger Jon M{\o}ller},
  journal={Annals of Medicine},
  pages={347 - 354}
CD163 is a hemoglobin scavenger receptor exclusively expressed in the monocyte‐macrophage system. A particularly high expression is seen in macrophages of the ‘alternative activation’ phenotype playing a major role in dampening the inflammatory response and in scavenging components of damaged cells. CD163‐mediated endocytosis of haptoglobin‐hemoglobin complexes formed upon red blood cell hemolysis leads to lysosomal degradation of the ligand protein and metabolism of heme by cytosolic heme… 
CD163 and inflammation: biological, diagnostic, and therapeutic aspects.
The scavenging of the oxidative and proinflammatory Hb leading to stimulation of the heme-oxygenase-1 and production of anti- inflammatory heme metabolites indicates that CD163 indirectly contributes to the anti-inflammatory response.
Tumor necrosis factor α‐converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163
The present results provide a likely explanation for the strong empirical relationship between the sCD163 plasma level and infectious/inflammatory diseases relating to macrophage activity.
CD163‐expressing monocytes constitute an endotoxin‐sensitive Hb clearance compartment within the vascular system
It is proposed that CD163‐mediated Hb‐Hp uptake by peripheral blood monocytes constitutes an Hb-Hp clearance pathway, which acts at the site of intravascular hemolysis to reduce Hb•Hp circulation time and toxicity.
Regulation of surface CD163 expression and cellular effects of receptor mediated hemoglobin‐haptoglobin uptake on human monocytes and macrophages
It is found that increased availability of HbHp complexes triggers the upregulation of surface CD163, and also results in a dose‐dependent secretion of IL‐6 and IL‐10.
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.
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.
The mononuclear phagocyte system in homeostasis and disease: a role for heme oxygenase-1.
Heme oxygenase-1 expression appears to regulate the homeostatic activity and distribution of mononuclear phagocytes in lymphoid tissue under physiological conditions and regulates the ability of MP to modulate the inflammatory response to tissue injury.
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.
Targeting the Hemoglobin Scavenger receptor CD163 in Macrophages Highly Increases the Anti-inflammatory Potency of Dexamethasone
A new biodegradable anti-CD163 antibody-drug conjugate is developed that specifically targets the glucocorticoid, dexamethasone to the hemoglobin scavenger receptor CD163 in macrophages and demonstrates CD163 as an excellent macrophage target for anti-inflammatory drug delivery.


Endotoxin induces rapid metalloproteinase‐mediated shedding followed by up‐regulation of the monocyte hemoglobin scavenger receptor CD163
It is shown that CD163 is rapidly mobilized in response to bacterial endotoxin, and studies using the inhibitor TAPI‐0 indicate that a metalloproteinase is responsible for LPS‐mediated shedding of CD163.
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.
Induction of the CD163‐dependent haemoglobin uptake by macrophages as a novel anti‐inflammatory action of glucocorticoids
It is shown that dexamethasone strongly induced the specific uptake of haemoglobin–haptoglobin complexes, CD163 mRNA transcription and cell surface expression by human macrophages, and proposed the augmentation of Hb clearance as a novel anti‐inflammatory action of glucocorticoids.
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.
Soluble CD163 inhibits phorbol ester-induced lymphocyte proliferation.
A potential direct anti-inflammatory effect mediated by soluble CD163 is identified and statistically significantly inhibits phorbol ester-induced human T-lymphocyte activation, thus attenuating the immune response to the inflammatory mediator.
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.
Identification of the haemoglobin scavenger receptor
The identification of the acute phase-regulated and signal-inducing macrophage protein, CD163, as a receptor that scavenges haemoglobin by mediating endocytosis of haptoglobin–haemoglobin complexes is reported.
Shedding of CD163, a novel regulatory mechanism for a member of the scavenger receptor cysteine-rich family.
It is suggested that PMA-induced activation of PKC leads to protease-mediated shedding of CD163, indicating a specific release mechanism of soluble CD163 by human monocytes which could play an important role in modulating inflammatory processes.
Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice
In murine macrophages, IL-10 induces expression of heme oxygenase-1 (HO-1), a stress-inducible protein with potential anti-inflammatory effect, via a p38 mitogen-activated protein kinase-dependent pathway, which provides new possibilities for improved therapeutic approaches for treating inflammatory diseases.