Pathophysiological, Cellular, and Molecular Events of the Vascular System in Anaphylaxis

Abstract

Anaphylaxis is a systemic hypersensitivity reaction that can be life threatening. Mechanistically, it results from the immune activation and release of a variety of mediators that give rise to the signs and symptoms of this pathological event. For years, most of the research in anaphylaxis has focused on the contribution of the immune component. However, approaches that shed light on the participation of other cellular and molecular agents are necessary. Among them, the vascular niche receives the various signals (e.g., histamine) that elicit the range of anaphylactic events. Cardiovascular manifestations such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and cardiac alterations are crucial in the pathophysiology of anaphylaxis and are highly involved to the development of the most severe cases. Specifically, the endothelium, vascular smooth muscle cells, and their molecular signaling outcomes play an essential role downstream of the immune reaction. Therefore, in this review, we synthesized the vascular changes observed during anaphylaxis as well as its cellular and molecular components. As the risk of anaphylaxis exists both in clinical procedures and in routine life, increasing our knowledge of the vascular physiology and their molecular mechanism will enable us to improve the clinical management and how to treat or prevent anaphylaxis.Key MessageAnaphylaxis, the most severe allergic reaction, involves a variety of immune and non-immune molecular signals that give rise to its pathophysiological manifestations. Importantly, the vascular system is engaged in processes relevant to anaphylactic events such as increased vascular permeability, vasodilation, hypotension, vasoconstriction, and decreased cardiac output. The novelty of this review focuses on the fact that new studies will greatly improve the understanding of anaphylaxis when viewed from a vascular molecular angle and specifically from the endothelium. This knowledge will improve therapeutic options to treat or prevent anaphylaxis.

Anaphylaxis: Mediators, Biomarkers, and Microenvironments

“…This is caused by the simultaneous activation of multiple molecular mechanisms and the sudden release of mediators which give rise to the signs and symptoms of this pathological event [26]. From years, studies have been focused on the analysis of the immune component, although the importance of other altered systems in the etiopathogenesis of anaphylaxis has been demonstrated [27,28]. Likely, other cells, still unexplored, contribute to the release of these or other mediators (TABLE 1).…”

“…The cardiovascular system is closely related to the pathophysiology of anaphylaxis [130,131]. A recent detailed review exhibits the vascular disorders accounting in this event where an acute increase in vascular permeability, relaxation of vascular smooth muscle and constriction of vessels in the thoracic cavity happen [27].…”

“…Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) interact with each other and govern the vascular pathophysiological processes of anaphylactic reactions [27,115].…”

“…On the other hand, VSMCs are responsible for the regulation of vascular tone through their contractile properties. This process is mainly modulated by changes in intracellular calcium levels and membrane depolarizations [27,141,142]. In anaphylaxis, mediators act on these cells causing relaxing or contractile processes in both bronquial and vascular smooth muscle cells [115].…”

Mast Cell Desensitization in Allergen Immunotherapy

“…Anaphylaxis severity is correlated to MC degranulation and the release of pro-inflammatory mediators ( 50 – 52 ). Intriguingly, anaphylactic mediators such as histamine are released during AIT without induction of anaphylaxis ( 53 , 54 ), which insinuates that a certain level of MC activation may be required to achieve desensitization. MC desensitization is accomplished during the early-phase of AIT, and studies in murine models support that this process directs the immunological outcome of AIT ( 30 ).…”