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.
Highlights
It is known that purinergic signaling is involved in various immune responses (Cekic and Linden, 2016; Cronstein and Sitkovsky, 2017)
Receptor expression level may play a critical role in mast cell activation and release of both newly synthesized cytokines and chemokines and stored mediators that are implicated in mast cell mediated allergic and inflammatory reactions in asthma. It seems that the differences between LAD2 and HMC-1 in terms of degranulation are mainly related to the expression level of FCεRI, tryptase and chymase, and to a much lesser extent related to histamine content or c-Kit expression (Guhl et al, 2010)
The authors suggest that A3AR, as a potentiator of FcεRI-induced degranulation, may involve a bronchoconstrictive response to adenosine in asthmatics, but not dermatologic allergy responses
Summary
Recent evidence showed that many other receptors, such as G protein-coupled receptors and ligand-gated ion channels, are 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. 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.
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