Tumor necrosis factor α‐converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163

  title={Tumor necrosis factor $\alpha$‐converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163},
  author={Anders Etzerodt and Maciej Bogdan Maniecki and Kirsten M{\o}ller and Holger Jon M{\o}ller and S{\o}ren Kragh Moestrup},
  journal={Journal of Leukocyte Biology},
CD163 is expressed specifically in the monocyte/macrophage lineage, where it mediates uptake of haptoglobin‐hemoglobin complexes, leading to metabolism of the oxidative heme molecule. Shedding of the CD163 ectodomain from the cell surface produces a sCD163 plasma protein, and a positive correlation is seen between the sCD163 plasma level and the severity of various infectious and inflammatory diseases. In the present analysis of the phorbol ester‐induced shedding of sCD163 in CD163 cDNA… 
Structural Basis for Inflammation-driven Shedding of CD163 Ectodomain and Tumor Necrosis Factor-α in Macrophages*
The present data indicate that CD163 underwent a modification that allows for an instant down-regulation of surface CD163 expression and inhibition of hemoglobin uptake and this regulatory modality seems to have coincided with the evolution of an enhanced hemoglobin-protecting role of the haptoglobin-CD163 system in primates.
Structural Basis for Inflammation-Driven Shedding of CD163 and Tumor Necrosis Factor-α in Macrophages
The present data indicate that CD163, by incorporation of this motif in late evolution, undervent a modification that allows for an instant downregulation of surface CD163 expression and inhibition of hemoglobin uptake, as well as an essential substrate motif for ADAM17-mediated CD163 and proTNF-α cleavage in macrophages.
The macrophage‐related biomarkers sCD163 and sCD206 are released by different shedding mechanisms
It is shown that in contrast to CD163, LPS‐mediated shedding of CD206 in humans is slow and a result of indirect signaling, which indicates that CD163 and CD206 are shed from the macrophages by very different mechanisms potentially involving distinctive inflammatory processes.
Soluble Scavenger Receptor CD163 Is Associated with Severe Acute Kidney Injury in Patients with Hantaan Virus Infection.
The correlations between plasma s CD163 and renal dysfunction suggest that sCD163 is an important player in the pathogenesis of hemorrhagic fever with renal syndrome.
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.
Soluble ectodomain CD163 and extracellular vesicle-associated CD163 are two differently regulated forms of ‘soluble CD163’ in plasma
The results show that soluble ectodomain CD163 and EV CD163 in plasma are part of separate macrophage response in the context of systemic inflammation.
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.
A disintegrin and metalloprotease 17 promotes microglial cell survival via epidermal growth factor receptor signalling following spinal cord injury
Investigating whether ADAM17-induced EGFR transactivation is involved in microglial cell survival following spinal cord injury (SCI) demonstrated thatADAM17 contributed to microglia cell survival, predominantly by EGFR signalling, following SCI.


Cross‐linking of FcγR triggers shedding of the hemoglobin‐haptoglobin scavenger receptor CD163
The presence of immune complexes in infection or autoimmunity may radically alter the nature of CD163‐dependent monocyte/macrophage processes, which may be particularly important in disease states in which immune complexes and high levels of free Hb are present.
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.
CD163: a regulated hemoglobin scavenger receptor with a role in the anti‐inflammatory response
Recent data indicate that solubleCD163 may be a valuable diagnostic parameter for monitoring macrophage activation in inflammatory conditions and a role for soluble CD163 in immune suppression has been proposed.
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.
Pivotal Advance: Activation of cell surface Toll‐like receptors causes shedding of the hemoglobin scavenger receptor CD163
It is demonstrated that the soluble HbSR is released from monocytic cells in response to TLR signaling as an acute innate immune response to extracellular pathogen infections.
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.
The ADAM metalloproteinases
The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria.
These findings identify CD163 as a macrophage receptor for bacteria and suggest that, during bacterial infection, CD163 on resident tissue macrophages acts as an innate immune sensor and inducer of local inflammation.
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.