Understanding the mechanisms of anaphylaxis

Abstract

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 (FcεRI), 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.

The role of sugammadex in the development and modification of an allergic response to rocuronium: evidence from a cutaneous model*

“…However, there is ample evidence that once mast cells are activated by an allergen, allergen-independent mechanisms are, at least in part, responsible for the propagation and amplification of the type-1 hypersensitivity reaction (e.g. tryptase, neuropeptides, sphingosine-1-phosphate, platelet activating factor, anaphylatoxins and the mast cell-leucocyte-cytokine cascade have all been shown to activate mast cells) [15][16][17][18][19].…”

Risk factors for anaphylaxis in patients with mastocytosis

“…However, the presence of KIT gene mutations, notably D816V, detectable in more than 90% of patients with SM resulting in an increased activation of the mast cells, does not correlate with the severity or the prevalence of anaphylaxis. 11 The simultaneous presence of allergy and myeloprolipheraptive disorders is observed also in hypereosinophilic syndromes. 12 There are scarce data on the frequency of anaphylactic reactions and their risk factors in patients with mastocytosis.…”

Drug‐induced anaphylaxis in the emergency room

“…As a consequence of mast cell and basophil activation by any of the above mechanisms, they release more than 100 chemical mediators of anaphylaxis. Initially, preformed mediators, including histamine, tryptase, carboxypeptidase A3, chymase, and proteoglycans are released 17, 18. These mediators trigger production of arachidonic acid metabolites, including prostaglandins and leukotrienes, and synthesis of platelet‐activating factor.…”