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The effect of inhibition of the processing of CD23 on IgE production in human and mouse cells and in a mouse model <jats:italic>in vivo<\/jats:italic> was evaluated. CD23 processing to sCD23 from RPMI 8866 (a human Epstein\u2010Barr virus\u2010transformed B cell line) cell membranes was inhibited by a broad\u2010spectrum matrix\u2010metalloprotease inhibitor, batimastat, with an IC<jats:sub>50<\/jats:sub> of 0.15 \u03bcM. Batimastat also inhibited CD23 processing in whole RPMI 8866 cells as well as in IL\u20104\u2010stimulated purified human monocytes with similar IC<jats:sub>50<\/jats:sub>. Batimastat inhibited IgE production from IL\u20104\/anti\u2010CD40\u2010stimulated human tonsil B cells as well as mouse splenic B cells in a manner consistent with inhibition of CD23 processing. Release of soluble fragments of CD23 in the cell supernatants of tonsil B cells was inhibited over the concentration range of 1\u201310 \u03bcM batimastat and intact cell surface CD23 was increased on mouse splenic B cells in the presence of these concentrations of batimastat. IgE production of IL\u20104\u2010stimulated human peripheral blood mononuclear cells was also blocked by 1\u201310 \u03bcM batimastat, again with comparable inhibition of sCD23 release over the same concentration range. Finally, in a mouse model of IgE production, batimastat inhibited IgE production in response to ovalbumin challenge as determined by serum IgE levels. Taken together, the data support a role of CD23 in IgE production and point to CD23 processing to sCD23 as a therapeutically relevant control point in the regulation of IgE synthesis.<\/jats:p>","DOI":"10.1002\/eji.1830271221","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T03:59:58Z","timestamp":1172807998000},"page":"3228-3235","source":"Crossref","is-referenced-by-count":35,"title":["IgE secretion is attenuated by an inhibitor of proteolytic processing of CD23 (Fc\u03b5RII)"],"prefix":"10.1002","volume":"27","author":[{"given":"Gary","family":"Christie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisling","family":"Barton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Bolognese","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek R.","family":"Buckle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard M.","family":"Cook","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Hansbury","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory P.","family":"Harper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa A.","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark E.","family":"McCord","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Moulder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul R.","family":"Murdock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheila M.","family":"Seal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivienne M.","family":"Spackman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beverley J.","family":"Weston","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth J.","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,6]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/366421a0"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1159\/000235067","volume":"90","author":"Wuthrich B.","year":"1989","journal-title":"Int. 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