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Regulation of IgE‐mediated signalling in human basophils by CD 32b and its role in Syk down‐regulation
Author(s) -
MacGlashan D.,
Moore G.,
Muchhal U.
Publication year - 2014
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12155
Subject(s) - syk , lyn , immunoglobulin e , phosphorylation , signalling , signal transduction , microbiology and biotechnology , biology , immunology , cancer research , proto oncogene tyrosine protein kinase src , antibody , tyrosine kinase
Summary Background CD 32b has been previously demonstrated to modulate IgE‐mediated secretion from human basophils. However, exploration of the implications of this regulation has been limited. One unstudied area is whether regulation of signalling by CD 32 also alters some of the phenotypic changes induced by IgE‐mediated activation. The reported character of CD 32‐mediated signal transduction is not clear for human basophils and the two primary mechanisms considered important in this reaction predict different long‐term outcomes, notably predicting different outcomes for down‐regulation of syk expression. Objective Syk expression was considered a unique point of phenotypic control in human basophils and the role of CD 32b in its regulation is explored in this study. However, initial pilot studies discovered that IL ‐3 could markedly up‐regulate CD 32 expression and first describing the consequences of this up‐regulation became an additional focus of this study. Methods Human basophils were examined for the changes in IgE‐mediated signalling during simultaneous engagement of CD 32b. Results Preliminary experiments noted that CD 32b could be up‐regulated by IL ‐3 (3‐ to 12‐fold). Both natural variation and induced up‐regulation of CD 32b modulated the efficacy of this receptor to inhibit IgE‐mediated release. Signalling induced by engagement of CD 32b (lyn, syk, SHP ‐1, or SHIP 1 phosphorylation) was more consistent with a mode of action involving SHIP 1 rather than SHP ‐1. IgE‐mediated down‐regulation of syk expression was not altered by co‐engagement of CD 32b, a result also consistent with a SHIP 1‐dependent mechanism of inhibition. Conclusions Taken together these results suggest that the combined action of IgE and IgG could generate a natural mechanism, whereby the significant variation in syk expression in allergic subjects occurs without necessarily also inducing mediator release.