Syk expression in peripheral blood leukocytes, CD34+ progenitors, and CD34-derived basophils

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Abstract
The critical signaling kinase of IgE-mediated reactions, syk, can be down-regulated in maturing basophils by chronic ag-gregation without altering their expression of FcRI, granule staining, and histamine content. In human basophils from different subjects, maximum IgE-mediated histamine release and the level of syk protein expression correlate well. It is not clear when in the basophil’s lifetime the set-point for syk expression is reached or how expression levels are determined for a given individual. An examination of syk expression in peripheral blood eosinophils, neutrophils, monocytes, B and T cells, DCs, and NK cells showed that with the exception of T cells, basophils were unique in expressing low levels of syk. No correlations were observed between syk expression in basophils and other types of leukocytes, suggesting a unique mechanism of regulation for basophils. The expression level of syk in CD34+ progenitors was ∼11-fold higher than in peripheral blood basophils, and it remained at this level during maturation of the cells in IL-3 to a cell with characteristics of peripheral blood basophils. Down-regulation of syk expression in the culture-derived basophils was induced by culturing under conditions of chronic aggregation of FcεRI. Syk was down-regulated to peripheral blood basophil levels in 50% of the cells. Despite the chronic aggregation of FcεRI, the cells retained the same expression of FcεRI, histamine content, and morphological staining of granules as cells not experiencing chronic aggregation. These results suggest that chronic stimulation through FcεRI during basophil maturation might be a mechanism for down-regulating syk expression, while retaining other characteristics associated with mature peripheral blood basophils.
Funding Information
  • National Institutes of Health (AI20253, AI070345)