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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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ADAM Proteins / immunology*
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ADAM Proteins / metabolism*
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ADAM10 Protein
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Amyloid Precursor Protein Secretases / immunology*
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Amyloid Precursor Protein Secretases / metabolism*
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Animals
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Electrophoresis, Polyacrylamide Gel
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Enzyme-Linked Immunosorbent Assay
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Fibroblasts / immunology
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Fibroblasts / metabolism
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Flow Cytometry
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Humans
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Immunoblotting
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Membrane Proteins / immunology*
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Membrane Proteins / metabolism*
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Mice
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Mice, Knockout
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Receptors, IgE / immunology*
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Receptors, IgE / metabolism*
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Transfection
Substances
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Membrane Proteins
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Receptors, IgE
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Amyloid Precursor Protein Secretases
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ADAM Proteins
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ADAM10 Protein
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Adam10 protein, mouse