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

被引：187

作者：

Etzerodt, Anders ^{[1
]}

Maniecki, Maciej Bogdan ^{[2
]}

Moller, Kirsten ^{[3
]}

Moller, Holger Jon ^{[2
]}

Moestrup, Soren Kragh ^{[1
,2
]}

机构：

[1] Univ Aarhus, Dept Med Biochem, DK-8000 Aarhus C, Denmark

[2] Aarhus Univ Hosp, Dept Clin Biochem, Aarhus C, Denmark

[3] Rigshosp, Univ Copenhagen Hosp, Dept Infect Dis, DK-2100 Copenhagen, Denmark

来源：

JOURNAL OF LEUKOCYTE BIOLOGY | 2010年 / 88卷 / 06期

基金：

英国医学研究理事会;

关键词：

endocytosis; hemoglobin; pathogenesis; sepsis; macrophage; SOLUBLE CD163; HUMAN MACROPHAGES; CROSS-LINKING; IDENTIFICATION; SURVIVAL; ANTIGEN;

D O I：

10.1189/jlb.0410235

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

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-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. J. Leukoc. Biol. 88: 1201-1205; 2010.

引用

页码：1201 / 1205

页数：5

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