Published online before print May 17, 2007
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
and its receptors by neutrophils and macrophagesDepartment of Veterinary and Biomedical Sciences, University of Minnesota, St. Paul, Minnesota, USA
1 Correspondence: University of Minnesota, 295j AS/VM Bldg., 1988 Fitch Avenue, St. Paul, MN 55108, USA. E-mail: walch003{at}umn.edu
ABSTRACT
TNF-
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-
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 proteases relative contribution to TNF-
, TNFRI, and TNFRII shedding using radiation chimeric mice with leukocytes lacking functional ADAM17. We report ablated, soluble TNF-
, TNFRI, and TNFRII production by neutrophils and macrophages stimulated with various microbial antigens and greatly reduced TNF-
levels in vivo following inflammation induction. This is the first simultaneous analysis of TNF-
, TNFRI, and TNFRII shedding by neutrophils and macrophages and the first direct evidence that ADAM17 is a primary and nonredundant sheddase.
Key Words: inflammation metalloprotease
This article has been cited by other articles:
![]() |
S. M. Le Gall, P. Bobe, K. Reiss, K. Horiuchi, X.-D. Niu, D. Lundell, D. R. Gibb, D. Conrad, P. Saftig, and C. P. Blobel ADAMs 10 and 17 Represent Differentially Regulated Components of a General Shedding Machinery for Membrane Proteins Such as Transforming Growth Factor {alpha}, L-Selectin, and Tumor Necrosis Factor {alpha} Mol. Biol. Cell, March 15, 2009; 20(6): 1785 - 1794. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Wang, A. H. Herrera, Y. Li, K. K. Belani, and B. Walcheck Regulation of Mature ADAM17 by Redox Agents for L-Selectin Shedding J. Immunol., February 15, 2009; 182(4): 2449 - 2457. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. A. Niewczas, L. H. Ficociello, A. C. Johnson, W. Walker, E. T. Rosolowsky, B. Roshan, J. H. Warram, and A. S. Krolewski Serum Concentrations of Markers of TNF{alpha} and Fas-Mediated Pathways and Renal Function in Nonproteinuric Patients with Type 1 Diabetes Clin. J. Am. Soc. Nephrol., January 1, 2009; 4(1): 62 - 70. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Hartl, C. H. He, B. Koller, C. A. Da Silva, R. Homer, C. G. Lee, and J. A. Elias Acidic Mammalian Chitinase Is Secreted via an ADAM17/Epidermal Growth Factor Receptor-dependent Pathway and Stimulates Chemokine Production by Pulmonary Epithelial Cells J. Biol. Chem., November 28, 2008; 283(48): 33472 - 33482. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Ponnuchamy and R. A. Khalil Role of ADAMs in Endothelial Cell Permeability: Cadherin Shedding and Leukocyte Rolling Circ. Res., May 23, 2008; 102(10): 1139 - 1142. [Full Text] [PDF] |
||||
![]() |
K. Horiuchi, T. Kimura, T. Miyamoto, H. Takaishi, Y. Okada, Y. Toyama, and C. P. Blobel Cutting Edge: TNF-{alpha}-Converting Enzyme (TACE/ADAM17) Inactivation in Mouse Myeloid Cells Prevents Lethality from Endotoxin Shock J. Immunol., September 1, 2007; 179(5): 2686 - 2689. [Abstract] [Full Text] [PDF] |
||||