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Beschreibung

Scavenger receptor cysteine-rich type 1 protein M130 (UniProt: Q86VB7, also known as Hemoglobin scavenger receptor, CD163) is encoded by the CD163 (also known as M130) gene (Gene ID: 9332) in human. CD163 is a single-pass type I membrane protein that is synthesized with a signal peptide (aa 1-41), which is subsequently cleaved off to produce the mature form that contains a long extracellular domain (aa 42-1050), a transmembrane domain (aa 1051-1071), and a cytoplasmic domain (aa 1072-1156). The extracellular domain contains nine scavenger receptor cysteine-rich (SRCR) scavenger receptor class B domains of about 100 amino acids each. SRCR domain 3 mediates calcium-sensitive interaction with Hemoglobin/Haptoglobin (Hb/Hp) complexes. CD163 is expressed in monocytes and mature macrophages with high expression observed in bone marrow macrophages, Kupffer cells, lung macrophages, and red pulp macrophages. Its levels are up regulated by anti-inflammatory mediators and suppressed by pro-inflammatory mediators like lipopolysaccharides (LPS) and TNF . It serves as an acute phase-regulated receptor involved in clearance and endocytosis of Hb/Hp complexes by macrophages and protects tissues from free hemoglobin-mediated oxidative damage. The binding of the Hb/Hp complex to CD163 macrophages leads to a fast degradation of the complex. CD163 also plays a role in the uptake and recycling of iron, via endocytosis of Hb/Hp complex and subsequent breakdown of heme. A soluble form of CF163 (sCD163) has also been described that is produced by proteolytic shedding and can be induced by LPS, phorbol ester, and Fc region of immunoglobulin . This soluble form plays an anti-inflammatory role and is considered a diagnostic parameter for monitoring macrophage activation in inflammatory conditions. Its expression is markedly induced by anti- inflammatory mediators, such as glucocorticoids and interleukin 10. Clone MAC2-158 binds to SRCR domain 1 of CD163 and recognizes over 80% of circulating CD14-expressing monocytes. (Ref.: Zhi, Y., et al. (2017). Mol. Med. Rep. 15(5), 2931-2939, Maniecki, MB., et al. (2011). Immunology 216(8), 882-890, Morganelli, PM., and Guyre, PM. (1988). J. Immunol. 140(7), 2296-2304).