FcγRI-mediated activation of human mast cells promotes survival and induction of the pro-survival gene Bfl-1

Activation of mast cells through either FcεRI or FcγRI leads to release of mediators contributing to the inflammatory response. One of the biologic characteristics of mast cells in allergic pathology is that these cells have the capacity to recover and regranulate after aggregation of FcεRI. We have previously demonstrated that the pro-survival protein A1/Bfl-1 is required for mast cells to survive IgE-mediated activation. In the present study, we have investigated whether human mast cells show similar induction of bfl-1 and activation-induced survival after aggregation of FcγRI. Human cord blood-derived mast cells were activated by aggregation of either FcεRI or FcγRI, and activation-induced survival and induction of bfl-1 was measured. We found that aggregation of FcγRI-induced expression of bf-1 and caused a comparable activation-induced mast cell survival as FcεRI does. These data suggests that activation through Fc-receptors contribute to mast cell survival during antibody-dependent mast cell mediated inflammatory responses.