TGF Presence During IgE-dependent Sensitization Primes Mast Cells for Higher VEGF Production After Fc RI Activation

Binding of monomeric Immunoglobulin E (IgE) to the high affinity IgE receptor (Fc RI) on mast cells induces a sensitization process which increases cell survival, augments membrane receptor expression and diminishes activation threshold. Although IgE-dependent sensitization is fundamental for allergic reactions, little is known about the influence of locally produced mediators on the outcome of a posterior allergen challenge. Since Transforming Growth Factor � (TGF) is an important immunomodulator present in most of the tissues where mast cells reside, we decided to analyze the consequences of TGF exposure during the sensitization step of mast cells on a posterior IgE-antigen stimulation. Bone Marrow-derived Mast Cells (BMMCs) were sensitized with IgE in the presence or absence of TGF. Then, antigen was added and the secretion of the angiogenic cytokine Vascular Endothelial Growth Factor (VEGF) was determined. BMMCs sensitized with IgE+TGF showed an increased antigen-induced VEGF secretion compared to those sensitized with IgE alone. Sensitization with IgE+TGF did not modify membrane FcRI receptor expression neither altered anti- gen-induced degranulation of the cells. Although both IgE and IgE+TGF sensitized cells showed an increase in VEGF mRNA stabilization after antigen addition, VEGF mRNA half-life was longer in IgE+TGF sensitized cells. p38 MAPK inhibitor SB202196 blocked VEGF mRNA stabilization after antigen addition specially on IgE+TGF sensitized cells. These findings suggest that TGFpresence during the sensitization phase of mast cells can induce modifications to the Fc RI signal transduction system, provoking increased VEGF mRNA stabilization and protein secretion after IgE-antigen stimulation through a p38 MAPK-dependent mechanism.