Cell desensitization

The cross-linking of the IgE receptors on the basophil or mast cell causes the activation of enzymes that result in secretion of mediators. Some of these biochemical reactions also regulate the extent of the release reaction. This process is called cell desensitization. Experimentally, desensitization is initiated by addition of the secretagogue under conditions that do not result in secretion, and after a defined incubation period the permissive conditions are restored. Desensitization is an active process, blocked by some pharmacologic agents, and is secretagogue-specific. The IgE receptor-mediated desensitization requires receptor aggregation, and can be either specific to the one antigen or for all IgE-mediated release reactions. At low cell surface IgE densities there is antigen-specific desensitization, whereas at high surface IgE levels there is desensitization for all IgE-mediated reactions. Desensitization is not due to the loss of cell surface antigen-specific IgE caused by endocytosis or shedding of IgE-antigen complexes. It is probably due to the decay of an unstable intermediate formed by the cross-linked receptors interacting with a secondary component. The degree of desensitization probably regulates the extent of the release process.

The mechanism for mediator release is similar in the various cell systems studied, e.g. human mast cells, basophils or rat mast cells. All systems respond to the physiologically relevant stimulus of IgE-anti-gen. However, there are differences in the response to miscellaneous secretagogues that could be related to the presence of surface receptors, and there are differences in the rate of release with various cells. Some pharmacologic agents inhibit release from human basophils but not from mast cells. There are differences in the spectrum of mediators released by mast cells compared with basophils. In contrast to mast cells, human basophils release very little, if any, of the cyclo-oxygenase-derived products of arachi-donic acid such as prostaglandin D2. However, both mast cells and basophils release the leukotriene C4. Mast cells but not basophils release the enzyme tryp-tase. There is little evidence to suggest that the secretory process is fundamentally different in the basophils compared with that in the mast cells.

See also: Allergens; Anaphylatoxins; Arachidonic acid and the leukotrienes; Exocytosis; Histamine; Hypersensitivity reactions; IgE; Interleukin 3; Plate-let-activating factor (PAF); Serotonin.

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