The tyrosine kinases p53/56lyn and p72syk are differentially expressed at the protein level but not at the messenger RNA level in nonreleasing human basophils.

Within the general population, individuals can be found whose basophils do not secrete after stimulation through the immunoglobulin (Ig) E receptor. In this study we compared two groups of donors, those whose basophils responded with 65+/-16% histamine release to an optimal concentration of anti-IgE antibody and those whose basophil response was not statistically different from nonstimulated release (1+/-1%). We show that these so-called nonreleasing basophils have at least 10-fold lower expression of the tyrosine kinases, lyn and syk, but normal expression of the tyrosine kinase Btk when compared with the panel of releasing basophils. Indeed, maximum histamine release correlated with expression of both syk (Spearman rank correlation coefficient [Rs] = 0.98) and lyn (Rs = 0.93). In contrast, equivalent levels of messenger RNA (mRNA) for lyn and syk kinase were found for both groups. By sequencing a critical region in the syk mRNA, our results also demonstrate that the frame shift mutation in syk leading to a premature stop codon which has been observed in other cell types is not present in nonreleasing human basophils. Our results suggest that there may be translational or post-translational regulatory mechanisms specific to the expression of two important FcepsilonRI-associated signaling elements in basophils.

The effect of tyrosine kinase inhibitors on IgE-mediated histamine release from human lung mast cells and basophils.

OBJECTIVE AND DESIGN: To investigate the role of tyrosine kinases (TK) in IgE-mediated signal transduction in human lung mast cells (HLMC) and basophils. MATERIALS: Peripheral blood basophils (n > or = 4) and human lung mast cells (n > or = 6). TREATMENT: Cells were preincubated with TK inhibitor for 15 min at 37 degrees C, before the addition of anti-IgE. METHODS: Histamine release (HR) was assayed using a fluorimetric technique. Results were compared using nonparametric statistics. RESULTS: Piceatannol and ST638 significantly (p < or = 0.05) inhibited anti-IgE induced HR from HLMCs and basophils whilst lavendustin C had no effect in either cell type. Herbimycin A also significantly (p < or = 0.05) inhibited anti-IgE induced HR from both cell types, an effect which was dose dependent but did require a 16 h preincubation with drug. CONCLUSIONS: In summary, HLMCs and basophils exhibit distinct inhibitory profiles in the presence of various inhibitors of TK.