TY - JOUR
T1 - Tumor necrosis factor α-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163
AU - Etzerodt, Anders
AU - Maniecki, Maciej Bogdan
AU - Møller, Kirsten
AU - Møller, Holger Jon
AU - Moestrup, Søren Kragh
PY - 2010
Y1 - 2010
N2 - 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-alpha 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
AB - 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-alpha 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
M3 - Journal article
SN - 0741-5400
VL - 88
SP - 1201
EP - 1205
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 6
ER -