Fc gamma RI-mediated activation of human mast cells promotes survival and induction of the pro-survival gene Bfl-1.

Activation of mast cells through either FcepsilonRI or FcgammaRI 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 FcepsilonRI. 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 FcgammaRI. Human cord blood-derived mast cells were activated by aggregation of either FcepsilonRI or FcgammaRI, and activation-induced survival and induction of bfl-1 was measured. We found that aggregation of FcgammaRI-induced expression of Bfl-1 and caused a comparable activation-induced mast cell survival as FcepsilonRI does. These data suggests that activation through Fc-receptors contribute to mast cell survival during antibody-dependent mast cell mediated inflammatory responses.