Sialylation modulates basophil responsiveness to galectin-3-dependent activation.

Basophils secrete histamine and IL-4/13 when cocultured with human lung adenocarcinoma cells (A549 cells). Previous studies have revealed that this interaction is dependent on galectin-3 expression on the surface of A549 cells (EC-Gal-3), IgE present on the surface of IL-3 primed basophils, and direct physical interaction between the two cell types, indicating a cognate interaction between IgE and Gal-3. Reciprocal secretion of protumorigenic cytokines (IL-6/VEGF-A) from A549 cells also results. Here, we further define the biological parameters required for this mode of activation. EC-Gal-3 stimulus has ∼20-fold less IgE crosslinking capacity compared with standard anti-IgE. The capacity of IgE-bearing basophils to elicit an EC-Gal-3-mediated response correlates with their responsiveness to standard anti-IgE stimulation, which is known to vary widely among individuals. However, unlike standard anti-IgE stimulation, basophil releasability in response to EC-Gal-3 is influenced by glycosylation patterns on surface-bound IgE. Specifically, bulk sialylation on IgE molecules suppress cellular releasability. Whole-cell basophil sialylation also suppresses EC-Gal-3 mediated activation. Gal-3 is an endogenous lectin with multivalent binding capacity and is implicated in a range of diseases involving immune modulation, organ fibrosis, and tumor metastasis. These results can help identify specific physiological and pathophysiological conditions by which IgE:Gal-3 interactions drive disease processes including wound healing, cancer, and fibrosis, including that which occurs in asthma.