title: ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23.
abstract: CD23, the low-affinity immunoglobulin E receptor, is an important modulator of the allergic response and of diseases such as rheumatoid arthritis. The proteolytic release of CD23 from cells is considered a key event in the allergic response. Here we used loss-of-function and gain-of-function experiments with cells lacking or overexpressing candidate CD23-releasing enzymes (ADAM8, ADAM9, ADAM10, ADAM12, ADAM15, ADAM17, ADAM19 and ADAM33), ADAM-knockout mice and a selective inhibitor to identify ADAM10 as the main CD23-releasing enzyme in vivo. Our findings provide a likely target for the treatment of allergic reactions and set the stage for further studies of the involvement of ADAM10 in CD23-dependent pathologies.
authors.affiliation: Arthritis and Tissue Degeneration Program, Hospital for Special Surgery and Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Gisela
authors.initials: G
authors.lastname: Weskamp
authors.forename: Jill W
authors.initials: JW
authors.lastname: Ford
authors.forename: Jamie
authors.initials: J
authors.lastname: Sturgill
authors.forename: Steve
authors.initials: S
authors.lastname: Martin
authors.forename: Andrew J P
authors.initials: AJ
authors.lastname: Docherty
authors.forename: Steven
authors.initials: S
authors.lastname: Swendeman
authors.forename: Neil
authors.initials: N
authors.lastname: Broadway
authors.forename: Dieter
authors.initials: D
authors.lastname: Hartmann
authors.forename: Paul
authors.initials: P
authors.lastname: Saftig
authors.forename: Shelby
authors.initials: S
authors.lastname: Umland
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sehara-Fujisawa
authors.forename: Roy A
authors.initials: RA
authors.lastname: Black
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: J David
authors.initials: JD
authors.lastname: Becherer
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Conrad
authors.forename: Carl P
authors.initials: CP
authors.lastname: Blobel
mesh_terms: D051722:ADAM Proteins / Q000276:immunology* / Q000378:metabolism*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism*; D014162:Transfection
chemical_list: D008565:Membrane Proteins; D017455:Receptors, IgE; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse