FceRI anaphylaxis

It is generally accepted (based on clinical and in vitro studies) that mast cells (and basophils), IgE and FceRI are involved in most cases of allergen-induced anaphylaxis in humans. However, it is difficult to define the exact roles and relative importance of mast cells, basophils, and other potential effector cells (e.g monocytes/macrophages, dendritic cells) in either IgE-dependent or IgE-independent human anaphylaxis. Unlike in mice, we neither have access to mast cell- or basophil-deficient humans nor can we genetically manipulate human subjects to produce such phenotypes. 

Adding another layer of complexity to the regulation of mast cell activation levels in vivo is the observation that activated mast cells can respond to, and in some cases produce, a myriad of mediators that may serve to amplify FceRI-induced responses. For example, stem cell factor (SCF), the ligand for KIT, both can enhance FceRI-dependent activation of mouse or human mast cells and, under certain circumstances, can directly induce mast cell degranulation [6, 25, 62]. Thus, elevated SCF levels and/or activating KIT mutations (such as those that occur in mastocytosis) may exacerbate mast cell-driven reactions. Indeed, patients (both adult and children) with extensive skin disease associated with mastocytosis are at increased risk to develop severe anaphylaxis [63]. Moreover, it was recently reported that cases of idiopathic anaphylaxis are... 

Galli SJ, Kinet JP Absence of FceRI a chain results in upregulation of FcyRIII-dependent mast cell degranulation and anaphylaxis. Evidence of competition between FceRI and FcyRIII for limiting amounts of FcR (3 and y chains. J Clin Invest 1997 32 99 915-925. 

HHMC have FceRI and IgE bound to their membrane surface and C5a receptors. Therefore it is likely that IgE- and C5a-mediated activation of these cells plays some part in systemic and cardiac anaphylaxis in man. 

Mast cells express high-affinity IgE Fc receptors (FceRI) on their surface, contain cytoplasmic granules which are major sources of histamine and other inflammatory mediators, and are activated to release and generate these mediators by IgE-dependent and non-IgE-dependent mechanisms [1]. Disturbances either in the release of mast cell mediators or in mast cell proliferation are associated with clonal mast cell disorders including monoclonal mast cell activation syndrome (MMAS) and mastocytosis respectively, which are in turn associated with some cases of anaphylaxis [2], Molecular mechanisms have been identified which may link increased releasability of mast cell mediators and conditions leading to increased mast cell numbers [3]. Patients with mastocytosis have an increased risk to develop anaphylaxis [4, 5] and those with anaphylaxis may suffer from unrecognized mastocytosis or may display incomplete features of the disease [6-8]. 

In contrast to the Miyajima et al. (34) report of FceRI-independent induction of anaphylaxis, Dombrowicz et al. (45) showed that FceRI is requisite for the induction of anaphylaxis. Lack of FceRI did not affect mast cell development, nor did it affect the half-life of IgE. FceRI receptor-deficient mice were protected from anaphylaxis and had no tachycardia, body temperature drop, or Evans Blue... 

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