Purinergic Signaling in Mast Cell Degranulation and Asthma

Abstract

Mast cells are responsible for the majority of allergic conditions. It was originally thought that almost all allergic events were mediated directly only via the high-affinity immunoglobulin E receptors. However, recent evidence showed that many other receptors, such as G protein-coupled receptors and ligand-gated ion channels, are also directly involved in mast cell degranulation, the release of inflammatory mediators such as histamine, serine proteases, leukotrienes, heparin, and serotonin. These mediators are responsible for the symptoms in allergic conditions such as allergic asthma. In recent years, it has been realized that purinergic signaling, induced via the activation of G protein-coupled adenosine receptors and P2Y nucleotide receptors, as well as by ATP-gated P2X receptors, plays a significant role in mast cell degranulation. Both adenosine and ATP can induce degranulation and bronchoconstriction on their own and synergistically with allergens. All three classes of receptors, adenosine, P2X and P2Y are involved in tracheal mucus secretion. This review will summarize the currently available knowledge on the role of purinergic signaling in mast cell degranulation and its most relevant disease, asthma.

Urinary and exhaled biomarkers of exercise‐induced bronchoconstriction in atopic asthmatic children

“…38 The wide distribution and the complex interrelation of ATP and adenosine in several body tissues including the lung, have been recently summarized. 39,40 Because the production of both adenosine and exhaled NO share the Th2-celldriven pathway, analyses for these substances to assess EIB could be only applicable in atopic patients.…”

“…9 Purinergic-membrane receptors for ATP (7 P2x and 8 P2y subunits) and four receptors for adenosine (A 1 , A 2A , A 2B , and A 3 ) are present in virtually all immunity cells. 9,39 Through several of these receptors both adenosine and ATP can induce mast cell degranulation by alone or enhancing the allergen-induced degranulation with the consequent release of histamine and inflammatory mediators. 39 We used a known indirect airway challenge, i., exercise, whose mechanism involves hyperosmotic damage of airway-epithelial cells during hyperventilation with subsequent release of inflammatory mediators and bronchial hyperreactivity.…”

“…ATP and adenosine are endogenous signaling molecules which closely interplay in inflammation and immunity to drive immune responses, either pro‐inflammatory or downregulating the airway injury . Purinergic‐membrane receptors for ATP (7 P2x and 8 P2y subunits) and four receptors for adenosine (A 1 , A 2A , A 2B , and A 3 ) are present in virtually all immunity cells . Through several of these receptors both adenosine and ATP can induce mast cell degranulation by alone or enhancing the allergen‐induced degranulation with the consequent release of histamine and inflammatory mediators …”

Mast cells—Good guys with a bad image?

“…58,59 Furthermore, this receptor plays an important role in the protection of the organism against parasitic infections. 66 It was long thought that all allergic reactions are based solely on an IgEdependent activation of MCs. 63 The IgE-dependent activation of MCs is associated with different diseases like allergic reactions, including asthma and the most severe form of allergic reactions, anaphylaxis.…”

“…[60][61][62] However, in case of chronic urticarial, the α-chain of the FcεRI receptor is attacked by autoantibodies. 66,67 FcεRI-mediated responses are also regulated by the presence of specific ligands such as prostaglandin E2, SCF, Toll-like receptor ligands, IL-33, as well as ligands of G protein-coupled receptors such as adenosine, macrophage inflammatory protein 1α, and RANTES that stimulate responses to antigen resulting in an augmented degranulation or cytokine production. 22,64,65 Degranulation of MCs leads to the secretion of vasoactive and inflammatory mediators that are the reason for symptoms.…”