Xanthone Jacareubin inhibits FcɛRI-dependent degranulation in mast cells by the blockage of extracellular calcium entry

• Published in: The Journal of immunology (1950) 2018-05, Vol.200 (1_Supplement), p.105-105.15
• Main Authors: Castillo-Arellano, Jorge Ivan, Guzmán-Gutiérrez, Silvia Laura, Ibarra-Sánchez, Alfredo, Hernández-Ortega, Simón, Reyes-Chilpa, Ricardo, Gonzalez-Espinosa, Claudia
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.105.15

Mast cells are important effectors in allergic reactions since they produce a number of pre-formed and de novo synthesized inflammatory compounds in response to high affinity IgE receptor (FcɛRI) crosslinking. IgE/Antigen-dependent degranulation and cytokine synthesis of this cell type have been recognized as relevant pharmacological targets for the control of deleterious inflammatory reactions. Despite the relevance of allergic diseases worldwide, pharmacological control of mast cell degranulation has not been achieved. In this work we analyzed the effect of the natural xanthone jacareubin on the main activation parameters of this cell type utilizing bone marrow-derived mast cells (BMMCs). Jacareubin, the xanthone obtained from the heartwood of the tropical tree Callophyllum brasilense, showed no toxicity when tested on bone marrow-derived mast cells (BMMCs) and did not activate degranulation by itself. However, jacareubin inhibited IgE/Ag-induced degranulation (determined as the secretion of β-hexosaminidase) in a dose-response manner (IC50 = 46 nM). Jacareubin blocked FcɛRI-dependent reactive oxygen species (ROS) formation, intracellular calcium mobilization and calcium-dependent protein kinase C (PKC) phosphorylation. Detailed analysis suggest that at least one of the molecular actions of jacareubin relies on the inhibition of plasma membrane calcium channels involved in degranulation of mast cells. It is proposed to jacareubin as a natural drug with antioxidant activity and a regulator of calcium channels, with prophylactic potential for the treatment of allergies produced by mast cells.