Reviews and feature articleMechanisms of mast cell signaling in anaphylaxis
Section snippets
Mast cell mediators and mechanisms of release
Anaphylaxis occurs rapidly and systemically, affecting 1 or more organ systems, generally where mast cells reside in relative abundance.2, 7 Underlying the pathophysiology of anaphylaxis is exposure to allergen or other factors that activate mast cells or basophils, prompting degranulation and immediate (5-30 minutes) release of preformed mediators (histamine, tryptase, carboxypeptidase A, and proteoglycans), synthesis of arachidonic acid metabolites (prostaglandins, leukotrienes), and
Mast cell signaling
The signaling cascades that regulate mast cell activation have been extensively investigated during the past few years and are described in depth in recent reviews.21, 22, 23 In this review the basic principles involved in the regulation of mast cell activation are described relative to the anaphylactic response and focus on the contributions of degranulation and immediately released mediators. The relevance of these studies to our understanding of the role of basophils in anaphylaxis is not
Conclusion
Advances in mast cell signaling research have improved our understanding of the pathophysiology of anaphylaxis. The identification of signaling pathways and components that amplify signals or alter the threshold of activation of mast cells, leading to degranulation and mediator release, has the promise of identifying novel approaches for prevention and treatment of anaphylaxis. The discovery of polymorphisms and mutations in components that regulate mast cell signaling might lead to ways to
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(Supported by an educational grant from Merck & Co., Inc.)
Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD
Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
Terms in boldface and italics are defined in the glossary on page 640.