Molecular consequences of human mast cell activation following immunoglobulin E–high-affinity immunoglobulin E receptor (IgE–FcϵRI) interaction

Systemic exacerbation of allergic responses, in which mast cells play a critical role, results in life-threatening anaphylactic shock. Sphingosine-1–phosphate (S1P), a ligand for a family of G protein–coupled receptors, is a new addition to the repertoire of bioactive lipids secreted by activated mast cells. Yet little is known of its role in human mast cell functions and in anaphylaxis. We show that S1P2 receptors play a critical role in regulating human mast cell functions, including degranulation and cytokine and chemokine release. Immunoglobulin E–triggered anaphylactic responses, including elevation of circulating histamine and associated pulmonary edema in mice, were significantly attenuated by the S1P2 antagonist JTE-013 and in S1P2-deficient mice, in contrast to anaphylaxis induced by administration of histamine or platelet-activating factor. Hence, S1P and S1P2 on mast cells are determinants of systemic anaphylaxis and associated pulmonary edema and might be beneficial targets for anaphylaxis attenuation and prophylaxis.

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The Emerging Picture of Mast Cell Activation: The Complex Regulatory Network of High-Affinity Receptor for Immunoglobulin E Signaling

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.b17-00465 ◽

2017 ◽

Vol 40 (11) ◽

pp. 1828-1832 ◽

Cited By ~ 3

Author(s):

Ryo Suzuki

Keyword(s):

Mast Cell ◽

Regulatory Network ◽

Cell Activation ◽

Immunoglobulin E ◽

Mast Cell Activation ◽

High Affinity ◽

High Affinity Receptor ◽

Affinity Receptor ◽

Complex Regulatory Network

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Human mast cell activation through Fc receptors and Toll-like receptors

Allergology International ◽

10.1111/j.1440-1592.2004.00338.x ◽

2004 ◽

Vol 53 (3) ◽

pp. 227-233 ◽

Cited By ~ 5

Author(s):

Yoshimichi Okayama ◽

Shigeru Okumura ◽

Hisashi Tomita ◽

Hiroko Katayama ◽

Keisuke Yuki ◽

...

Keyword(s):

Mast Cell ◽

Cell Activation ◽

Fc Receptors ◽

Mast Cell Activation ◽

Human Mast Cell ◽

Toll Like Receptors

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Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction

International Journal of Molecular Sciences ◽

10.3390/ijms19124092 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4092 ◽

Cited By ~ 1

Author(s):

Chen Shao ◽

Bingjie Fu ◽

Ning Ji ◽

Shunli Pan ◽

Xiaoxia Zhao ◽

...

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Allergic Reaction ◽

Nuclear Factor Kappa B ◽

Immunoglobulin E ◽

Mast Cell Activation ◽

Human Mast Cell ◽

Dependent Manner ◽

Nuclear Factor ◽

Nuclear Factor Kappa

Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A2 (MAPK/cPLA2). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.

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The Role Played by Mitochondria in FcεRI-Dependent Mast Cell Activation

Frontiers in Immunology ◽

10.3389/fimmu.2020.584210 ◽

2020 ◽

Vol 11 ◽

Author(s):

Maria A. Chelombitko ◽

Boris V. Chernyak ◽

Artem V. Fedorov ◽

Roman A. Zinovkin ◽

Ehud Razin ◽

...

Keyword(s):

Mast Cell ◽

Transcription Factors ◽

Mast Cells ◽

Cell Activation ◽

Immunoglobulin E ◽

Mitochondrial Dynamics ◽

Allergic Diseases ◽

Mast Cell Activation ◽

Basic Knowledge ◽

Mitochondrial Activity

Mast cells play a key role in the regulation of innate and adaptive immunity and are involved in pathogenesis of many inflammatory and allergic diseases. The most studied mechanism of mast cell activation is mediated by the interaction of antigens with immunoglobulin E (IgE) and a subsequent binding with the high-affinity receptor Fc epsilon RI (FcεRI). Increasing evidences indicated that mitochondria are actively involved in the FcεRI-dependent activation of this type of cells. Here, we discuss changes in energy metabolism and mitochondrial dynamics during IgE-antigen stimulation of mast cells. We reviewed the recent data with regards to the role played by mitochondrial membrane potential, mitochondrial calcium ions (Ca2+) influx and reactive oxygen species (ROS) in mast cell FcεRI-dependent activation. Additionally, in the present review we have discussed the crucial role played by the pyruvate dehydrogenase (PDH) complex, transcription factors signal transducer and activator of transcription 3 (STAT3) and microphthalmia-associated transcription factor (MITF) in the development and function of mast cells. These two transcription factors besides their nuclear localization were also found to translocate in to the mitochondria and functions as direct modulators of mitochondrial activity. Studying the role played by mast cell mitochondria following their activation is essential for expanding our basic knowledge about mast cell physiological functions and would help to design mitochondria-targeted anti-allergic and anti-inflammatory drugs.

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The Downregulation of Mast Cell Activation Through the Suppression of the High-Affinity IgE Receptor Expression by Green Tea Catechin Egcg

Basic and Applied Aspects ◽

10.1007/978-90-481-3892-0_50 ◽

2010 ◽

pp. 301-306

Author(s):

Hirofumi Tachibana ◽

Yoshinori Fujimura ◽

Yusuke Hasegawa ◽

Satomi Yano ◽

Koji Yamada

Keyword(s):

Mast Cell ◽

Green Tea ◽

Cell Activation ◽

Receptor Expression ◽

Mast Cell Activation ◽

Ige Receptor ◽

High Affinity ◽

Green Tea Catechin ◽

High Affinity Ige Receptor

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Alpha7-nicotinic acetylcholine receptors involve the imidacloprid-induced inhibition of IgE-mediated rat and human mast cell activation

RSC Advances ◽

10.1039/c7ra07862e ◽

2017 ◽

Vol 7 (82) ◽

pp. 51896-51906 ◽

Cited By ~ 5

Author(s):

Linbo Shi ◽

Huaping Xu ◽

Yujie Wu ◽

Xin Li ◽

Li Zou ◽

...

Keyword(s):

Mast Cell ◽

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Cell Activation ◽

Mast Cell Activation ◽

Human Mast Cell ◽

Inhibition Mechanism ◽

Nicotinic Acetylcholine ◽

Neonicotinoid Insecticide ◽

Ige Mediated

Although our recent study indicated that imidacloprid, a widely used neonicotinoid insecticide, inhibited IgE-mediated mast cell activation, the inhibition mechanism still remains unclear.

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