Mast cell

Mast cells arise from bone-marrow progenitors (CD34⁺, KIT⁺) that circulate in an immature form and complete their maturation inside tissues under the influence of stem-cell factor (the ligand for the KIT receptor). They are large oval cells with a round, central nucleus and cytoplasm crowded with metachromatic granules containing histamine, heparin, the proteases tryptase (a specific marker) and chymase, and preformed TNF-α. They sit at the body's interfaces with the environment — in the dermis, airway and gut mucosa and around blood vessels and nerves — and live for months to years. Two subtypes are recognised in humans: mucosal mast cells (tryptase only) and connective-tissue mast cells (tryptase and chymase).

Mast cells are coated with IgE through the high-affinity receptor FcεRI (sensitisation). Cross-linking of that IgE by multivalent allergen triggers a three-stage response: within seconds–minutes, degranulation releases histamine and tryptase (vasodilatation, increased vascular permeability, itch, bronchoconstriction, mucus secretion); within minutes, synthesis of lipid mediators — prostaglandin D2, leukotrienes C4/D4/E4 (the "slow-reacting substance of anaphylaxis") and platelet-activating factor; and over hours, production of cytokines (IL-4, IL-5, IL-13, TNF-α) that recruit eosinophils and Th2 cells in the late-phase reaction. Mast cells can also be activated independently of IgE, by complement anaphylatoxins (C3a, C5a), neuropeptides (substance P) and certain drugs (opioids, vancomycin, radiocontrast, some neuromuscular blockers).