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.
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We thank V. Nikolenko and A. Shirazi for technical assistance; recombinant mouse IL-4 was a gift from W. Paul (US National Institutes of Health). Supported by the US National Institutes of Health (GM64750 to C.P.B and AI18697 to D.H.C.), the US National Institute of Allergy and Infectious Diseases (T32 AI07407 to J.W.F.) and the National Institutes of Health National Center for Research Resources Research Facilities Improvement Program (C06-RR12538-01 for construction of the facility housing the laboratory of C.P.B.).
A.D., N.B., S.U., R.A.B. and J.D.B. are employed by pharmaceutical companies. Antibody 30X is the subject of patent WO 99/58679 (“Antibodies to CD23, derivatives thereof, and their therapeutic uses”).
Generation of the humanized CD23 mAb 30X and specificity control. (PDF 934 kb)
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