Scavenger receptors play important roles in homeostasis and innate immunity by binding to endogenous and foreign molecules. Scavenger receptors on the plasma membrane of macrophages bind to ligand and allow their internalization and can also mediate pro- or anti-inflammatory signaling. The plasma membrane glycoprotein CD163 is a member of the scavenger receptor cysteine-rich (SRCR) protein family. CD163 contains nine SRCR domains and is expressed in macrophages and monocytes where it plays a role in innate immunity and regulation of inflammation in response to ligand binding. CD163 binds specifically to hemoglobin (Hb)-haptoglobin (Hp) complexes produced during hemolysis to allow their internalization and lysosomal degradation. Additionally, CD163 has been shown to bind other ligands including some bacterial or viral pathogens. Recognition of these ligands leads to internalization and breakdown as well as context dependent cytokine release. Membrane-bound and secreted forms of CD163 are increased under pathological conditions and may serve as a marker for inflammation or disease.
The Takeya group sought to generate monoclonal antibodies to identify anti-inflammatory macrophages (1). One of their antibodies served as an effective marker of inflammatory macrophages in various species. Through mass spectrometry and immunoprecipitation with the CD163 antibody they were able to confirm their identified antibody binds to a CD163 antigen. The Sorg group performed experiments to identify CD163 functions apart from binding of hemoglobin (Hb)-haptoglobin (Hp) (2). By using the CD163 antibody to affinity purify recombinant CD163 they were able to treat cells with soluble CD163 and follow the response. Soluble CD163 showed anti-inflammatory effects on transcription and surface marker gene expression. Melino et al. from the University of Queensland used the CD163 antibody for immunofluorescence to examine liver biopsies from patients with chronic hepatitis C (3). In their study CD163+ macrophages expressed matrix metalloproteinase-9 and may contribute to hepatocyte dysfunction. Like CD163, CD68 has been used as a marker for macrophages and monocytes. The Moriconi group demonstrated CD68 is also expressed in neutrophil granulocytes (NGs) (4). They used the CD163 antibody for immunofluorescence to distinguish CD68+ NGs from CD68+ cells internalized by macrophages. The Holt group for Rockefeller University examined obesity associated inflammation and colorectal cancer risk (5). They used the CD163 antibody for immunohistochemistry to assess macrophage numbers and inflammation in patient biopsies. Diet induced weight loss reduced inflammation and decreased the risk of cancer.
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