Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis

Klein, Ofir; Sagi‐Eisenberg, Ronit

doi:10.1155/2019/9542656

Cited by 32 publications

(22 citation statements)

References 145 publications

(182 reference statements)

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“…Some proteins required for its proper function are Ca 2+ -sensitive. Such proteins include Munc13-4, synaptotagmin II, and double C2 (Doc2α) (61)(62)(63).…”

Section: Calcium Signalingmentioning

confidence: 99%

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

et al. 2020

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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 (Ca 2+) 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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“…Some proteins required for its proper function are Ca 2+ -sensitive. Such proteins include Munc13-4, synaptotagmin II, and double C2 (Doc2α) (61)(62)(63).…”

Section: Calcium Signalingmentioning

confidence: 99%

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

et al. 2020

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“…Immune-regulated exocytosis uses SNAP23 and VAMP8 whereas SNAP25 and VAMP1 and VAMP2 are used in neuronal signalling 15 . Degranulation has been studied mainly in murine mast cells and the RBL cell line, as these can be cultured in sufficient quantities 16 . IgE-mediated activation is an example of a bi-or multivalent activation mechanism through adaptive immune signalling.…”

Section: Basophil Signalling In Ige-mediated Basophil Degranulationmentioning

confidence: 99%

Basophil activation test: mechanisms and considerations for use in clinical trials and clinical practice

Santos

Alpan

Hoffmann

2020

Preprint

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The basophil activation test (BAT) is a functional assay that measures the degree of degranulation following stimulation with allergen or controls by flow cytometry and is directly correlated with histamine release. From the bell-shaped curve resulting from BAT in allergic patients, basophil reactivity (given by %CD63+ basophils) and basophil sensitivity (given by EC50 or similar) are the main outcomes of the test. BAT takes into account all characteristics of IgE and allergen and thus can be more specific than sensitization tests in the diagnosis of allergic disease. BAT reduces the need for in vivo procedures, such as intradermal tests and allergen challenges, which can cause allergic reactions of unpredictable severity. As it closely reflects the patients' phenotype, it can potentially be used to monitor the natural resolution of food allergies and to predict and monitor clinical response to immunomodulatory treatments, such as allergen-specific immunotherapy and biologicals. Clinical application of BAT requires analytical validation, clinical validation, standardization of procedures and quality assurance to ensure reproducibility and reliability of results. Currently, efforts are ongoing to establish a platform that could be used by laboratories in Europe and in the USA for certification.

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“…One of the most distinguishing morphological features of MCs is represented by MC granules that occupy almost the entire cytoplasm, appear electron-dense, and contain considerable amounts of bioactive molecules ready to be released upon MC stimulation. They encapsulate various mediators such as proteases, cytokines, chemokines, amines (e.g., histamine and serotonin), and enzymes including the β-hexosaminidase [ 31 , 32 ].…”

Section: MC Subsets and Heterogenous Functional Specializationmentioning

confidence: 99%

FcεRI Signaling in the Modulation of Allergic Response: Role of Mast Cell-Derived Exosomes

Lecce

Molfetta

Milito

et al. 2020

IJMS

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Mast cells (MCs) are immune cells that act as environment resident sentinels playing a crucial role in Th2-mediated immune responses, including allergic reactions. Distinguishing features of MCs are the presence of numerous cytoplasmic granules that encapsulate a wide array of preformed bio-active molecules and the constitutive expression of the high affinity receptor of IgE (FcεRI). Upon FcεRI engagement by means of IgE and multivalent antigens, aggregated receptors trigger biochemical pathways that ultimately lead to the release of granule-stored and newly synthesized pro-inflammatory mediators. Additionally, MCs are also able to release exosomes either constitutively or upon stimulation. Exosomes are nanosized vesicles of endocytic origin endowed with important immunoregulatory properties, and represent an additional way of intercellular communication. Interestingly, exosomes generated upon FcεRI engagement contain co-stimulatory and adhesion molecules, lipid mediators, and MC-specific proteases, as well as receptor subunits together with IgE and antigens. These findings support the notion that FcεRI signaling plays an important role in influencing the composition and functions of exosomes derived by MCs depending on their activation status.

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Anaphylactic Degranulation of Mast Cells: Focus on Compound Exocytosis

Cited by 32 publications

References 145 publications

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

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

Basophil activation test: mechanisms and considerations for use in clinical trials and clinical practice

FcεRI Signaling in the Modulation of Allergic Response: Role of Mast Cell-Derived Exosomes

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