Changes in syk expression in human basophils (HB) induced by a non-IgE-dependent receptor, LIR7 (38.9)

Abstract

Abstract Expression of syk in HB is highly variable among subjects and correlates with the ability of the cell to respond to FceRI aggregation. Because evidence suggests a post-translational influence on syk expression, we sought ways that syk could be down-regulated by the activation of non-IgE-dependent receptors. HB express LIR7 and aggregation of LIR7 induces mediator secretion kinetically similar to IgE-mediated release. These studies test whether aggregation of LIR7 reduces expression of syk and whether LIR7 operates through syk to induce histamine release (HR). HB were stimulated with mouse anti-LIR7 and anti-mouse Ab (the combination abbreviated to: aLIR7) and assessed for syk phosphorylation and for changes in syk expression. HR was examined ± the presence of a third generation syk inhibitor. aLIR7 induced syk phosphorylation and a modest loss of syk in 18 hour cultures (14±5% loss, n=11, p=0.013) compared to anti-IgE (53±10% loss). There was a correlation between the amount of syk loss induced by anti-IgE and the loss induced by aLIR7 (r=0.63). There was a correlation, r=0.97, between HR induced by anti-IgE and that induced by aLIR7 (means= 43%&25%). The IC50 for inhibition of aLIR7-induced HR was 0.2 μM (IC50 for anti-IgE was 0.038 μM). Each of these data sets is consistent with a dependence of LIR7 signaling on syk and shows that a non-IgE-dependent stimulus can alter syk expression levels. Supported NIH-AI20253