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Age-Induced Reprogramming of Mast Cell Degranulation¹

Department of Genetics, University of North Carolina, Chapel Hill, NC 27599

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 PGE₂ during inflammation. We show that although PGE₂ does not trigger the degranulation of dermal mast cells of young animals, in older mice, PGE₂ is a potent mast cell stimulator. Intradermal administration of PGE₂ 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 PGE₂ to initiate mast cell degranulation changes in the aging animal. Therefore, elevated PGE₂ levels might provide an important pathway by which mast cells are engaged to participate in inflammatory responses in the elderly patient.