ADAMs10/17 deficient mast cells exhibit decreased IgE-mediated activation in vitro .

Allergies and asthma are common ailments that are on the rise around the world. Mast cells play a direct role in the signs and symptoms characteristic in allergic patients. The family of A Disintegrin And Metalloproteinases (ADAMs) are involved in regulating many cellular processes by cleaving surface receptors, ligands, and signaling molecules. We sought to determine the role of ADAMs10/17 in bone marrow-derived mast cell (BMMC) activity. In dual inhibitor-based studies, percent degranulation and cytokines released by IgE-mediated activation were significantly reduced. Interestingly, ionomycin-activation was unchanged with inhibitor treatment, suggesting that ADAMs10/17 may be involved in IgE-mediated mast cell activation upstream of calcium influx. Preliminary results with ADAM17 MC−/− BMMCs have confirmed the inhibitor data and provided interesting results regarding increased mast cell survival and proliferation. These data suggest that targeting ADAMs10/17 could attenuate mast cell-related T H 2 responses.