Age-induced reprogramming of mast cell degranulation

Mast cell degranulation can initiate an acute inflammatory response and contribute to the progression of chronic diseases. Alteration in the cellular programs that determine the requirement for mast cell degranulation would therefore have the potential to dramatically impact disease severity. Mast cells are exposed to increased levels of PGE(2) during inflammation. We show that although PGE(2) does not trigger the degranulation of dermal mast cells of young animals, in older mice, PGE(2) is a potent mast cell stimulator. Intradermal administration of PGE(2) leads to an EP3 receptor-dependent degranulation of mast cells, with the number of degranulated cells approaching levels observed in IgE- and Ag-treated controls. Taken together, these studies suggest that the ability of PGE(2) to initiate mast cell degranulation changes in the aging animal. Therefore, elevated PGE(2) levels might provide an important pathway by which mast-cells are engaged to participate in inflammatory responses in the elderly patient.