Understanding the Mechanisms of Anaphylaxis

Richard D. Peavy; Dean D. Metcalfe


Curr Opin Allergy Clin Immunol. 2008;8(4):310-314. 

In This Article

Abstract and Introduction

Purpose of Review: The present review considers recent reports that identify the roles of key intermediate signaling components and mediators during and after mast cell activation and degranulation leading to anaphylaxis.
Recent Findings: Mechanisms of anaphylaxis are becoming better understood as the interaction of several regulatory systems in the mast cell activation and degranulation signaling cascade. Multiple tyrosine kinases, activated after immunoglobulin E binding to the high-affinity receptors for immunoglobulin E (FcRI), exert both positive and negative regulation on the signaling cascade, which may vary with genetic background or mutations in signaling proteins. Calcium influx, the essential, proximal intracellular event leading to mast cell degranulation, is controlled also by both negative and positive regulation through calcium channels. Sphingosine-1-phosphate is emerging as a newly realized mediator of anaphylaxis, acting as a signaling component within the mast cell and as a circulating mediator.
Summary: Anaphylaxis is a systemic reaction involving multiple organ systems, but it is believed that it may be influenced by cellular events in mast cells and basophils resulting in the release of mediators. Therefore, understanding the mechanisms of mast cell activation and degranulation is critical to understanding the mechanisms of anaphylaxis. Recent reports have identified important regulatory components of the signaling cascade and, consequently, potential targets for therapeutic intervention.

Anaphylaxis is a systemic reaction involving multiple organ systems. It is most frequently associated with exposure to allergens and the release of mediators from mast cells and basophils. Anaphylaxis may potentially lead to death, although this is not the usual outcome. The sudden and often unanticipated onset and the catastrophic physiological impact of anaphylaxis make proper diagnosis and appropriate treatment critical to beneficial outcomes. Since the first description of anaphylaxis by Portier and Richet[1] over a century ago, anaphylaxis has been recognized as both a dangerous and a puzzling disease. No less confounding has been the absence of consensus on definitions and diagnostic criteria, and clear insight into underlying pathophysiologic mechanisms. Recent reports have addressed these issues by proposing diagnostic criteria, identifying key chemical mediators, and identifying key intermediates contributing to mast cell and basophil activation.


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