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IgE secretion is attenuated by an inhibitor of proteolytic processing of CD23 (Fc epsilonRII).

Abstract：

:CD23, the low-affinity IgE receptor, is up-regulated on interleukin (IL)-4-stimulated B cells and monocytes, with a concomitant increase in the release of soluble fragments of CD23 (sCD23) into the medium by proteolytic processing of the surface-bound intact CD23. The effect of inhibition of the processing of CD23 on IgE production in human and mouse cells and in a mouse model in vivo was evaluated. CD23 processing to sCD23 from RPMI 8866 (a human Epstein-Barr virus-transformed B cell line) cell membranes was inhibited by a broad-spectrum matrix-metalloprotease inhibitor, batimastat, with an IC50 of 0.15 microM. Batimastat also inhibited CD23 processing in whole RPMI 8866 cells as well as in IL-4-stimulated purified human monocytes with similar IC50. Batimastat inhibited IgE production from IL-4/anti-CD40-stimulated 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 1-10 microM 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-4-stimulated human peripheral blood mononuclear cells was also blocked by 1-10 microM 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.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Christie G,Barton A,Bolognese B,Buckle DR,Cook RM,Hansbury MJ,Harper GP,Marshall LA,McCord ME,Moulder K,Murdock PR,Seal SM,Spackman VM,Weston BJ,Mayer RJ

doi

10.1002/eji.1830271221

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

3228-35

issue

eissn

0014-2980

issn

1521-4141

journal_volume

pub_type

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IgE secretion is attenuated by an inhibitor of proteolytic processing of CD23 (Fc epsilonRII).