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  • Title: Tumor necrosis factor α-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163.
    Author: Etzerodt A, Maniecki MB, Møller K, Møller HJ, Moestrup SK.
    Journal: J Leukoc Biol; 2010 Dec; 88(6):1201-5. PubMed ID: 20807704.
    Abstract:
    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-transfected HEK293 cells, we used metalloproteinase inhibitors and siRNA-mediated inhibition of metalloproteinases to identify TACE/ADAM17 as an enzyme responsible for PMA-induced cleavage of the membrane-proximal region of CD163. As TACE/ADAM17-mediated shedding of TNF-α is up-regulated in macrophages subjected to inflammatory stimuli, the present results now provide a likely explanation for the strong empirical relationship between the sCD163 plasma level and infectious/inflammatory diseases relating to macrophage activity.
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