Tumor necrosis factor α-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163

Journal of Leukocyte Biology

Holger Jon Møller  and³  Maciej Bogdan Maniecki³  Anders Etzerodt¹  Søren Kragh Moestrup ¹  Kirsten Møller² 

[1] Departments of Medical Biochemistry, University of Aarhus, and  Clinical Biochemistry, Aarhus University Hospital, Aarhus C, Denmark;Department of Infectious Diseases, University Hospital Rigshospitalet, Copenhagen, Denmark  Clinical Biochemistry, Aarhus University Hospital, Aarhus C, Denmark; Clinical Biochemistry, Aarhus University Hospital, Aarhus C, Denmark;

关键词: endocytosis;    hemoglobin;    pathogenesis;    sepsis;    macrophage;   

DOI  :  10.1189/jlb.0410235

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown