Human and mouse mast cells express surface PrP that is shed upon activation and affects degranulation

Abstract Misfolded prion protein (PrP) is the causative infectious agent in prion diseases in both humans and animals. Despite this, the physiological role of PrP in its native conformation (PrPC) is still poorly understood. While best known for its presence on neurons, PrPC is also present on various immune cells. We determined whether mast cells also expressed surface PrPC and whether PrPC expression was linked to changes in mast cell function. Mast cells are tissue-resident immune cells that modulate many physiologic responses such as allergic inflammation, tissue remodeling, response to infection and neuroplasticity. When activated, mast cells degranulate rapidly, releasing several pre-formed signaling molecules and enzymes. We hypothesized that mast cells expressed PrP and that its expression was influenced by mast cell activation. Human (HMC-1 and LAD2) and rodent (BMMC) mast cell lines expressed surface PrPC with the highest expression in BMMC. Activation of mouse bone marrow derived mast cells (BMMC) with A23187 caused a 12 fold decrease in surface PrP expression after 30 min. Surprisingly, levels of PrP recovered to almost half of untreated levels 3 hrs post-stimulation, and reached similar levels to untreated by 48 hrs. BMMCs derived from PrP knockout mice activated by IgE/antigen released 15–25% less granule contents compared to wild type BMMC, suggesting that PrP is somehow involved in degranulation. There were no significant differences in cell surface expression of the IgE receptor FcɛRI in wild type and knockout BMMC. Our results indicate that PrP is highly expressed on human and rodent mast cells and that it may play an important role in degranulation and activation of mast cells, independent of FcɛRI expression.