ATP Mediated Mast Cell Activation is Female Dominant 2260259

Abstract Introduction Allergic diseases are more common in women than men. The explanation for this dimorphism is only partly understood. ATP is a damage associated molecular pattern (DAMP) that is elevated in allergic asthma. Mast cells are central to allergic inflammation and are central to DAMPs. We tested the hypothesis that female mast cells mount stronger responses than male mast cells when stimulated with ATP. Methods We cultured bone marrow derived mast cells from C57BL/6, C3HeJ, and BALB/c mice. Cells were stimulated with ATP, or ATP derivatives and mast cell cytokine responses were measured by ELISA and flow cytometry. Results ATP elicited greater cytokine release and degranulation in female mast cells than in male mast cells. This was not due to a difference in the expression of the ATP receptor, P2X7 between males and females. Because ATP has a short half-life, we tested the non-hydrolysable isoforms ATPγS and ADPβS, as well as adenosine. None of these ATP derivatives yielded a sexually dimorphic response. The dimorphic ATP response could therefore be due to differences in the rate of ATP degradation. In support of this hypothesis, male BMMCs express higher levels of the ATP degrading enzyme CD39. Conclusion Our data supports the hypothesis that female mast cells mount a stronger response to ATP. This difference may be due to female mast cells degrading ATP at a slower rate. Funding Source 1R01AI164710 Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)