RGD Reference Report - Role of ADAM17 in the ectodomain shedding of TNF-alpha and its receptors by neutrophils and macrophages. - Rat Genome Database

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Role of ADAM17 in the ectodomain shedding of TNF-alpha and its receptors by neutrophils and macrophages.

Authors: Bell, JH  Herrera, AH  Li, Y  Walcheck, B 
Citation: Bell JH, etal., J Leukoc Biol. 2007 Jul;82(1):173-6. Epub 2007 May 17.
RGD ID: 5129925
Pubmed: PMID:17510296   (View Abstract at PubMed)
DOI: DOI:10.1189/jlb.0307193   (Journal Full-text)

TNF-alpha and its receptors TNFRI and TNFRII are cleaved from the surface of leukocytes by a proteolytic process referred to as ectodomain shedding. The role of a disintegrin and metalloproteinase 17 (ADAM17) in this process by the major professional phagocytes neutrophils and macrophages, the primary producers of TNF-alpha during inflammation induction, is based entirely on indirect evidence, and other sheddases have been implicated as well. As Adam17 gene-targeting in mice is lethal, we assessed the protease's relative contribution to TNF-alpha, TNFRI, and TNFRII shedding using radiation chimeric mice with leukocytes lacking functional ADAM17. We report ablated, soluble TNF-alpha, TNFRI, and TNFRII production by neutrophils and macrophages stimulated with various microbial antigens and greatly reduced TNF-alpha levels in vivo following inflammation induction. This is the first simultaneous analysis of TNF-alpha, TNFRI, and TNFRII shedding by neutrophils and macrophages and the first direct evidence that ADAM17 is a primary and nonredundant sheddase.


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