Antigen Mediated Histamine Release

Specific antigen-antibody interactions initiate the degranulation of tissue mast cells and blood basophils as part of the immediate hypersensitivity reaction. Immunoglobulin E (IgE) antibodies (reaginic antibodies) directed against an allergenic substance attach to the outer surface of the cell membrane and initiate a series of biochemical events that culminate in the release of the secretory granule contents (Fig. 38.1). Although allergens are the most frequent initiators of immediate hypersensitivity reactions, certain drugs, particularly in association with endogenous high-molecular-weight molecules, may also promote the sensitization process and mast cell degranulation on subsequent drug exposure.

Certain endogenous and exogenous compounds modulate the antigen-mediated release of histamine from sensitized tissues. Histamine inhibits its own release in skin mast cells and blood basophils by binding to H2 histamine receptors, which when activated, inhibit degranulation. This feedback inhibition does not appear to occur in lung mast cells. Agonists of ^-adrenoceptors inhibit antigen-induced histamine release from mast cells, whereas muscarinic and a-adrenergic agonists enhance mast cell degranulation.

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