| First Author | Bell JH | Year | 2007 |
| Journal | J Leukoc Biol | Volume | 82 |
| Issue | 1 | Pages | 173-6 |
| PubMed ID | 17510296 | Mgi Jnum | J:122782 |
| Mgi Id | MGI:3715430 | Doi | 10.1189/jlb.0307193 |
| Citation | Bell JH, et al. (2007) Role of ADAM17 in the ectodomain shedding of TNF-{alpha} and its receptors by neutrophils and macrophages. J Leukoc Biol 82(1):173-6 |
| abstractText | 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. |
