Mast cell degranulation signaling pathway

The mast cell degranulation signaling pathway is a critical immune response mechanism primarily initiated by the cross-linking of the high-affinity IgE receptor (FcεRI) on the surface of mast cells by multivalent antigens (Yang et al., 2023; Research Goal, 2026). This event triggers a complex intracellular signaling cascade involving Src-family kinases (Lyn, Fyn), the spleen tyrosine kinase (Syk), and Bruton's tyrosine kinase (BTK), which collectively activate phospholipase C gamma (PLCγ) (Kim et al., 2023; ResearchGate, 2023). The subsequent generation of second messengers, such as inositol trisphosphate (IP3) and diacylglycerol (DAG), leads to a rapid rise in cytosolic calcium and the activation of protein kinase C (PKC), ultimately resulting in the exocytosis of preformed granules containing histamine, proteases, and heparin (Nutraceutical Aid, 2021; Semantic Scholar, 2022). This pathway also stimulates the de novo synthesis of lipid mediators (e.g., leukotrienes, prostaglandins) and various pro-inflammatory cytokines (Yang et al., 2023; ResearchGate, 2026). Dysregulation of this pathway is a hallmark of allergic diseases, including asthma, chronic urticaria, and systemic anaphylaxis, making its components attractive targets for therapeutic intervention (PubMed, 2023; ResearchGate, 2026). Current pharmacological approaches include the use of monoclonal antibodies to sequester IgE, mast cell stabilizers to prevent granule release, and small-molecule inhibitors targeting key signaling kinases like Syk and KIT (Kim et al., 2023; MDPI, 2023).

Other names

FcεRI signaling pathwayMast cell activation pathwayIgE-mediated degranulation pathwayMast cell degranulation cascade

Inhibition of IgE-FcεRI interaction, stabilization of mast cell membranes to prevent exocytosis, and targeted inhibition of intracellular signaling kinases such as Syk, BTK, and KIT to block the release of inflammatory mediators.