scholarly journals Mast cells and mastocytosis

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 946-956 ◽  
Author(s):  
Dean D. Metcalfe
Keyword(s):  
Mast Cells ◽  
Kinase Inhibitors ◽  
Allergic Inflammation ◽  
Host Responses ◽  
High Affinity ◽  
Human Mast Cells ◽  
Proinflammatory Mediators ◽  
High Affinity Receptor ◽  
Ige Mediated ◽  
Affinity Receptor

Abstract Mast cells have been recognized for well over 100 years. With time, human mast cells have been documented to originate from CD34+ cells, and have been implicated in host responses in both innate and acquired immunity. In clinical immunology, they are recognized for their central role in IgE-mediated degranulation and allergic inflammation by virtue of their expression of the high-affinity receptor for IgE and release of potent proinflammatory mediators. In hematology, the clinical disease of mastocytosis is characterized by a pathologic increase of mast cells in tissues, often associated with mutations in KIT, the receptor for stem cell factor. More recently, and with increased understanding of how human mast cells are activated through receptors including the high-affinity receptor for IgE and KIT, specific tyrosine kinase inhibitors have been identified with the potential to interrupt signaling pathways and thus limit the proliferation of mast cells as well as their activation through immunoglobulin receptors.

scholarly journals CD84 Negatively Regulates IgE High-Affinity Receptor Signaling in Human Mast Cells

2011 ◽  
Vol 187 (11) ◽  
pp. 5577-5586 ◽  
Author(s):  
Damiana Álvarez-Errico ◽  
Irene Oliver-Vila ◽  
Erola Ainsua-Enrich ◽  
Alasdair M. Gilfillan ◽  
César Picado ◽  
...  
Keyword(s):  
Mast Cells ◽  
Receptor Signaling ◽  
High Affinity ◽  
Human Mast Cells ◽  
High Affinity Receptor ◽  
Affinity Receptor

scholarly journals Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by FcεRIβ and the Potential Impact of FcεRIβ Splicing in Allergic Inflammation

2022 ◽  
Vol 23 (2) ◽  
pp. 788
Author(s):  
Greer K. Arthur ◽  
Glenn Cruse
Keyword(s):  
Mast Cells ◽  
Cell Function ◽  
Allergic Inflammation ◽  
Receptor Complex ◽  
Ige Receptor ◽  
Preferential Expression ◽  
High Affinity ◽  
Proinflammatory Mediators ◽  
Ige Mediated ◽  
High Affinity Ige Receptor

Mast cells are tissue-resident immune cells that function in both innate and adaptive immunity through the release of both preformed granule-stored mediators, and newly generated proinflammatory mediators that contribute to the generation of both the early and late phases of the allergic inflammatory response. Although mast cells can be activated by a vast array of mediators to contribute to homeostasis and pathophysiology in diverse settings and contexts, in this review, we will focus on the canonical setting of IgE-mediated activation and allergic inflammation. IgE-dependent activation of mast cells occurs through the high affinity IgE receptor, FcεRI, which is a multimeric receptor complex that, once crosslinked by antigen, triggers a cascade of signaling to generate a robust response in mast cells. Here, we discuss FcεRI structure and function, and describe established and emerging roles of the β subunit of FcεRI (FcεRIβ) in regulating mast cell function and FcεRI trafficking and signaling. We discuss current approaches to target IgE and FcεRI signaling and emerging approaches that could target FcεRIβ specifically. We examine how alternative splicing of FcεRIβ alters protein function and how manipulation of splicing could be employed as a therapeutic approach. Targeting FcεRI directly and/or IgE binding to FcεRI are promising approaches to therapeutics for allergic inflammation. The characteristic role of FcεRIβ in both trafficking and signaling of the FcεRI receptor complex, the specificity to IgE-mediated activation pathways, and the preferential expression in mast cells and basophils, makes FcεRIβ an excellent, but challenging, candidate for therapeutic strategies in allergy and asthma, if targeting can be realized.

scholarly journals IL-33 and Superantigenic Activation of Human Lung Mast Cells Induce the Release of Angiogenic and Lymphangiogenic Factors

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 145
Author(s):  
Leonardo Cristinziano ◽  
Remo Poto ◽  
Gjada Criscuolo ◽  
Anne Lise Ferrara ◽  
Maria Rosaria Galdiero ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Lung ◽  
Protein A ◽  
Protein L ◽  
Variable Regions ◽  
Prolonged Incubation ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Affinity Receptor ◽  
Pleiotropic Functions

Human lung mast cells (HLMCs) express the high-affinity receptor FcεRI for IgE and are strategically located in different compartments of human lung, where they play a role in several inflammatory disorders and cancer. Immunoglobulin superantigens (e.g., protein A of Staphylococcus aureus and protein L of Peptostreptococcus magnus) bind to the variable regions of either the heavy (VH3) or light chain (κ) of IgE. IL-33 is a cytokine expressed by epithelial cells that exerts pleiotropic functions in the lung. The present study investigated whether immunoglobulin superantigens protein A and protein L and IL-33 caused the release of inflammatory (histamine), angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors from HLMCs. The results show that protein A and protein L induced the rapid (30 min) release of preformed histamine from HLMCs. By contrast, IL-33 did not induce the release of histamine from lung mast cells. Prolonged incubation (12 h) of HLMCs with superantigens and IL-33 induced the release of VEGF-A and VEGF-C. Preincubation with IL-33 potentiated the superantigenic release of histamine, angiogenic and lymphangiogenic factors from HLMCs. Our results suggest that IL-33 might enhance the inflammatory, angiogenic and lymphangiogenic activities of lung mast cells in pulmonary disorders.

scholarly journals Evolutionary background of allergic reactivity: mast cells, FcεRI, IgE - three components of the effector phase of the allergic response

2018 ◽  
Vol 15 (4) ◽  
pp. 5-16
Author(s):  
I S Gushchin
Keyword(s):  
Mast Cells ◽  
Immunoglobulin E ◽  
The Body ◽  
Allergic Response ◽  
Effector Phase ◽  
Time Regime ◽  
High Affinity Receptor ◽  
Ige Mediated ◽  
Affinity Receptor ◽  
Elimination Function

The literature data on the evolution of the main obligatory participants in the effector phase of the IgE-mediated allergic response are presented: mast cells/basophils, immunoglobulin E, and high affinity receptor for the Fcε fragment (FcεRI). Allergic reactivity is considered as the most recent evolutionary immunologically-mediated acquisition of mammals. It is aimed at recognizing small amounts of allergen entering the body in a certain time regime, and organizing an allergen-specific inflammation that carries features of elimination function. The most biologically justified way to prevent allergies is to restore the function of barrier systems and, accordingly, to prevent the need to develop an allergic response.

scholarly journals Gender-Related Effects of Sex Steroids on Histamine Release and FcεRI Expression in Rat Peritoneal Mast Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Samira Muñoz-Cruz ◽  
Yolanda Mendoza-Rodríguez ◽  
Karen E. Nava-Castro ◽  
Lilián Yepez-Mulia ◽  
Jorge Morales-Montor
Keyword(s):  
Mast Cells ◽  
Histamine Release ◽  
Sex Steroids ◽  
Male Rats ◽  
Peritoneal Mast Cells ◽  
High Affinity Receptor ◽  
Ige Mediated ◽  
Affinity Receptor ◽  
And Gender ◽  
Pathologic Processes

Mast cells (MCs) are versatile effector and regulatory cells in various physiologic, immunologic, and pathologic processes. In addition to the well-characterized IgE/FcεRI-mediated degranulation, a variety of biological substances can induce MCs activation and release of their granule content. Sex steroids, mainly estradiol and progesterone, have been demonstrated to elicit MCs activation. Most published studies have been conducted on MCs lines or freshly isolated peritoneal and bone marrow-derived MC without addressing gender impact on MC response. Our goal was to investigate if the effect of estradiol, progesterone, testosterone, and dihydrotestosterone (DHT) on MCs may differ depending on whether female or male rats are used as MCs donors. Our results demonstrated that effect of sex steroids on MCs histamine release is dose- and gender-dependent and can be direct, synergistic, or inhibitory depending on whether hormones are used alone or to pretreat MCs followed by substance P-stimulation or upon IgE-mediated stimulation. In contrast, sex steroids did not have effect on the MC expression of the IgE high affinity receptor, FcεRI, no matter female or male rats were used. In conclusion, MCs degranulation is modulated by sex hormones in a gender-selective fashion, with MC from females being more susceptible than MC from males to the effects of sex steroids.

Soluble human high-affinity receptor for IgE abrogates the IgE-mediated allergic reaction

1993 ◽  
Vol 5 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Chisel Ra ◽  
Sadao Kuromitsu ◽  
Tomohiro Hirose ◽  
Shuhei Yasuda ◽  
Kiyoshi Furuich ◽  
...  
Keyword(s):  
Allergic Reaction ◽  
High Affinity ◽  
High Affinity Receptor ◽  
Ige Mediated ◽  
Affinity Receptor
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