ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23.
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.
Weskamp
Gisela
G
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.
Ford
Jill W
JW
Sturgill
Jamie
J
Martin
Steve
S
Docherty
Andrew J P
AJ
Swendeman
Steven
S
Broadway
Neil
N
Hartmann
Dieter
D
Saftig
Paul
P
Umland
Shelby
S
Sehara-Fujisawa
Atsuko
A
Black
Roy A
RA
Ludwig
Andreas
A
Becherer
J David
JD
Conrad
Daniel H
DH
Blobel
Carl P
CP
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
D008565:Membrane Proteins; D017455:Receptors, IgE; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse