Søren Kragh Moestrup

CD163 and inflammation: Biological, diagnostic and therapeutic aspects

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Significance: The hemoglobin 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 pro-inflammatory hemoglobin leading to stimulation of the heme-oxygenase-1 and production of anti-inflammatory heme metabolites indicate that CD163 thereby indirectly contributes to the anti-inflammatory response. Recent Advances: 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 arise from the increased shedding of CD163 mediated by the tumor necrosis factor-α (TNFα) 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 non-shed 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 hemoglobin-induced damages after blood transfusion. Critical issues and future directions The diagnostic and therapeutic properties of CD163 await further clinical studies and regulatory approval before implementation in the clinic.
Original languageEnglish
JournalAntioxidants & Redox Signaling
Pages (from-to)2352-2363
Publication statusPublished - 2013

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