CD163 and inflammation: biological, diagnostic, and therapeutic aspects.
CONCLUSIONS
The hemoglobin (Hb) scavenger receptor, CD163, is a macrophage-specific protein and the upregulated expression of this receptor is one of the major changes in the macrophage switch to alternative activated phenotypes in inflammation. Accordingly, a high CD163 expression in macrophages is a characteristic of tissues responding to inflammation. 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 thereby indirectly contributes to the anti-inflammatory response.


BACKGROUND
In addition to this biological role in inflammation, CD163 is a potential inflammation biomarker and a therapeutic target. The biomarker form of CD163 is the soluble plasma CD163 that arises from the increased shedding of CD163 mediated by the tumor necrosis factor-α (TNF-α) cleaving enzyme. This explains that a steadily increasing literature documents that the plasma level of soluble CD163 is increased in a large spectrum of acute and chronic inflammatory disorders. The nonshed membrane form of CD163 in macrophages constitutes a target for drugs to be directed to macrophages in inflammation. This approach has been used in an animal inflammation model to highly increase the apparent therapeutic index of anti-inflammatory glucocorticoid drug that was coupled to an anti-CD163 antibody. Furthermore, other recent animal data, which indirectly involve CD163 in macrophages, demonstrate that injections of haptoglobin attenuate Hb-induced damages after blood transfusion.


CONCLUSIONS
The diagnostic and therapeutic properties of CD163 await further clinical studies and regulatory approval before implementation in the clinic.
Department of Biomedicine, University of Aarhus, Aarhus C, Denmark.
Anders
A
Etzerodt
Søren K
SK
Moestrup
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D005786:Gene Expression Regulation; D006242:Haptoglobins / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D006242:Haptoglobins; D006454:Hemoglobins; D011956:Receptors, Cell Surface