Atopy and Role of Mast Cells in IgE-Mediated Allergic Diseases

2014 ◽  
Vol 9 (4) ◽  
pp. 249-260
Author(s):  
Guillermina Jiménez-Andrade
Keyword(s):  
Mast Cells ◽  
Allergic Diseases ◽  
Ige Mediated

scholarly journals Impaired FcϵRI stability, signaling, and effector functions in murine mast cells lacking glycosylphosphatidylinositol-anchored proteins

Blood ◽  
2011 ◽  
Vol 118 (16) ◽  
pp. 4377-4383 ◽  
Author(s):  
Wouter L. W. Hazenbos ◽  
Ping Wu ◽  
Jeffrey Eastham-Anderson ◽  
Taroh Kinoshita ◽  
Eric J. Brown
Keyword(s):  
Mast Cells ◽  
Targeted Disruption ◽  
Potential Therapeutic Target ◽  
Effector Functions ◽  
Ige Mediated ◽  
Interchain Interactions ◽  
Β Chain ◽  
Stimulation Of

Abstract A key event and potential therapeutic target in allergic and asthmatic diseases is signaling by the IgE receptor FcϵRI, which depends on its interactions with Src family kinases (SFK). Here we tested the hypothesis that glycosylphosphatidylinositiol-anchored proteins (GPI-AP) are involved in FcϵRI signaling, based on previous observations that GPI-AP colocalize with and mediate activation of SFK. We generated mice with a hematopoietic cell-specific GPI-AP deficiency by targeted disruption of the GPI biosynthesis gene PigA. In these mice, IgE-mediated passive cutaneous anaphylaxis was largely abolished. PigA-deficient mast cells cultured from these mice showed impaired degranulation in response to stimulation with IgE and antigen in vitro, despite normal IgE binding and antigen-induced FcϵRI aggregation. On stimulation of these cells with IgE and antigen, coprecipitation of the FcϵRI α-chain with the γ-chain and β-chain was markedly reduced. As a result, IgE/antigen–induced FcϵRI-Lyn association and γ-chain tyrosine phosphorylation were both impaired in PigA-deficient cells. These data provide genetic evidence for an unanticipated key role of GPI-AP in FcϵRI interchain interactions and early FcϵRI signaling events, necessary for antigen-induced mast cell degranulation.

scholarly journals Direct Inhibition of the Allergic Effector Response by Raw Cow’s Milk—An Extensive In Vitro Assessment

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1258
Author(s):  
Suzanne Abbring ◽  
Bart R. J. Blokhuis ◽  
Julie L. Miltenburg ◽  
Kiri G. J. Romano Olmedo ◽  
Johan Garssen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Allergic Diseases ◽  
Raw Milk ◽  
Mast Cell Activation ◽  
Cow’S Milk ◽  
Cow's Milk ◽  
Ige Mediated ◽  
Raw Cow’S Milk

The mechanisms underlying the allergy-protective effects of raw cow’s milk are poorly understood. The current focus is mainly on the modulation of T cell responses. In the present study, we investigated whether raw cow’s milk can also directly inhibit mast cells, the key effector cells in IgE-mediated allergic responses. Primary murine bone marrow-derived mast cells (BMMC) and peritoneal mast cells (PMC), were incubated with raw milk, heated raw milk, or shop milk, prior to IgE-mediated activation. The effects on mast cell activation and underlying signaling events were assessed. Raw milk was furthermore fractionated based on molecular size and obtained fractions were tested for their capacity to reduce IgE-mediated mast cell activation. Coincubation of BMMC and PMC with raw milk prior to activation reduced β-hexosaminidase release and IL-6 and IL-13 production, while heated raw milk or shop milk had no effect. The reduced mast cell activation coincided with a reduced intracellular calcium influx. In addition, SYK and ERK phosphorylation levels, both downstream signaling events of the FcεRI, were lower in raw milk-treated BMMC compared to control BMMC, although differences did not reach full significance. Raw milk-treated BMMC furthermore retained membrane-bound IgE expression after allergen stimulation. Raw milk fractionation showed that the heat-sensitive raw milk components responsible for the reduced mast cell activation are likely to have a molecular weight of > 37 kDa. The present study demonstrates that raw cow’s milk can also directly affect mast cell activation. These results extend the current knowledge on mechanisms via which raw cow’s milk prevents allergic diseases, which is crucial for the development of new, microbiologically safe, nutritional strategies to reduce allergic diseases.

Historical anecdotes and breakthroughs of histamine: from discovery to date

2020 ◽  
Vol 20 ◽  
Author(s):  
Ioannis Alexandros Charitos ◽  
Francesca Castellaneta ◽  
Luigi Santacroce ◽  
Lucrezia Bottalico
Keyword(s):  
Mast Cells ◽  
Treatment Guidelines ◽  
Allergic Diseases ◽  
History Of ◽  
Museum Archives ◽  
Ancient Times ◽  
New Research ◽  
Preclinical And Clinical Studies ◽  
Historical References

Aim: Investigating about the history of allergies and discovery of the histamine’s role in the immune response through historical references, starting with ancient anecdotes, analysing the first immunization attempts on animals to understand its importance as the anaphylaxis mediator. Moreover, we shortly resume the most recent discoveries on mast cell role in allergic diseases throughout the latest updates on its antibody-independent receptors. Methods: Publications, including reviews, treatment guidelines, historical and medical books, on the topic of interest were found on Medline, PubMed, Web of Knowledge, Web of Science, Google Scholar, Elsevier’s (EMBASE.comvarious internet museum archives. Texts from the National Library of Greece (Stavros Niarchos Foundation), from the School of Health Sciences of the National and Kapodistrian University of Athens (Greece). We selected key articles which could provide an historical and scientific insight into histamine molecule and its mechanism of action’s discovery starting with Egyptian, Greek and Chinese antiquity to end with the more recent pharmacological and molecular discoveries. Results: Allergic diseases were described by medicine since ancient times, without exactly understanding physio-pathologic mechanisms of immuno-mediated reactions and of their most important biochemical mediator, histamine. Researches on histamine and allergic mechanisms started at the beginning of the 20th century with the first experimental observations on animals of anaphylactic reactions. Histamine was then identified as their major mediator of many allergic diseases and anaphylaxis, but also of several physiologic body’s functions, and its four receptors were characterized. Modern researches focus their attention on the fundamental role of the antibody-independent receptors of mast cells in allergic mechanisms, such as MRGPRX2, ADGRE2 and IL-33 receptor. Conclusion: New research should investigate how to modulate immunity cells activity in order to better investigate possible multi-target therapies for host’s benefits in preclinical and clinical studies on allergic diseases in which mast cells play a major role.

Non-IgE Mediated Food Allergy

2020 ◽  
Vol 16 (2) ◽  
pp. 95-105
Author(s):  
Antonella Cianferoni
Keyword(s):  
Food Allergy ◽  
Eosinophilic Esophagitis ◽  
Allergic Diseases ◽  
Food Allergies ◽  
Food Protein ◽  
Ige Mediated ◽  
Food Challenges ◽  
Allergic Proctocolitis ◽  
Eosinophilic Disorders

Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in western countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody– mediated immune responses, there is an increasing recognition of cell-mediated disorders, such as eosinophilic esophagitis and food protein–induced enterocolitis. Non-IgE-Mediated gastrointestinal food allergies are a heterogeneous group of food allergies in which there is an immune reaction against food but the primary pathogenesis is not a production of IgE and activation of mast cells and basophils. Those diseases tend to affect mainly the gastrointestinal tract and can present as acute (FPIES) or chronic reaction, such as Eosinophilic Esophagitis (EoE), Food Protein-Induced Allergic Proctocolitis (FPIAP). The role of food allergy in Non-EoE gastrointestinal Eosinophilic disorders (Non- EoE EGID) is poorly understood. In some diseases like EoE, T cell seems to play a major role in initiating the immunological reaction against food, however, in FPIES and FPIAP, the mechanism of sensitization is not clear. Diagnosis requires food challenges and/or endoscopies in most of the patients, as there are no validated biomarkers that can be used for monitoring or diagnosis of Non-IgE mediated food allergies. The treatment of Non-IgE food allergy is dependent on diet (FPIES, and EoE) and/or use of drugs (i.e. steroids, PPI) in EoE and Non-EoE EGID. Non-IgE mediated food allergies are being being investigated.

Superior Immunomodulatory Effects of Cultured Mast Cells: Potent Strategy for Treatment of Gvhd

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4684-4684
Author(s):  
Raita Araki ◽  
Hideaki Maeba ◽  
Rie Kuroda ◽  
Toshihiro Fujiki ◽  
Shintaro Mase ◽  
...  
Keyword(s):  
Mast Cells ◽  
Acute Gvhd ◽  
Mixed Lymphocyte Reaction ◽  
Conflicts Of Interest ◽  
Tumor Development ◽  
Independent Manner ◽  
Hematopoietic Stem ◽  
Effector Cells ◽  
Ige Mediated

Abstract Abstract 4684 Mast cells have long been known as effector cells in the various IgE-mediated allergic responses. However, recent studies demonstrated that mast cells play various roles in immune reactions in coordination with other immune cells. That is, mast cells exert pro-inflammatory or anti-inflammatory effects depending on the situation. In addition, mast cells have association with tumor development. In allogeneic hematopoietic stem cell transplantation (HSCT), only a few have reported that the numbers of mast cells were correlated with the severity of acute GVHD in the skin. However, exact role of mast cells in GVHD remains unclear. With the purpose of potential application of mast cells in a clinical HSCT for GVHD, mixed lymphocyte reaction (MLR) was performed to clarify whether mast cells impaired the alloreaction or not. To generate bone marrow derived cultured mast cells (BMCMCs), BM cells from mice were incubated in complete RPMI containing IL-3 for 6 weeks. As shown in the figure, we showed that MLR was strongly inhibited when BMCMCs from the stimulator strain were added to the coculture (Stimulator (S): DCs obtained from C57BL/6, Responder (R): splenocytes from Balb/c, BMCMCs from C57BL/6). Next, when BMCMCs from the responder strain were added to the coculture, MLR was also suppressed (S: DCs obtained from C57BL/6, R: splenocytes from Balb/c, BMCMCs from Balb/c). In conclusion, mast cells suppressed lymphocyte proliferation induced by allo-DCs in an MHC-independent manner. Just like mesenchymal stem cells, cell therapy utilizing cultured mast cells may reduce GVHD severity. Disclosures: No relevant conflicts of interest to declare.

Role of mast cells in the onset of IgE-mediated late-phase cutaneous response in mice

2000 ◽  
Vol 106 (1) ◽  
pp. S91-S98 ◽  
Author(s):  
Hiroichi Nagai ◽  
Toru Abe ◽  
Itaru Yamaguchi ◽  
Kanako Mito ◽  
Masako Tsunematsu ◽  
...  
Keyword(s):  
Mast Cells ◽  
Late Phase ◽  
Ige Mediated ◽  
Cutaneous Response

scholarly journals Bacterial and Fungal Toll-Like Receptor Activation Elicits Type I IFN Responses in Mast Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Lisa Kornstädt ◽  
Sandra Pierre ◽  
Andreas Weigert ◽  
Stefanie Ebersberger ◽  
Tim J. Schäufele ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cell ◽  
Mast Cells ◽  
Allergic Diseases ◽  
Receptor Activation ◽  
Type I ◽  
Toll Like Receptor ◽  
Resolution Of Inflammation ◽  
Type I Ifns ◽  
Ige Mediated

Next to their role in IgE-mediated allergic diseases and in promoting inflammation, mast cells also have antiinflammatory functions. They release pro- as well as antiinflammatory mediators, depending on the biological setting. Here we aimed to better understand the role of mast cells during the resolution phase of a local inflammation induced with the Toll-like receptor (TLR)-2 agonist zymosan. Multiple sequential immunohistology combined with a statistical neighborhood analysis showed that mast cells are located in a predominantly antiinflammatory microenvironment during resolution of inflammation and that mast cell-deficiency causes decreased efferocytosis in the resolution phase. Accordingly, FACS analysis showed decreased phagocytosis of zymosan and neutrophils by macrophages in mast cell-deficient mice. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which is known to enhance phagocytosis by macrophages. Both, zymosan and lipopolysaccharides (LPS) induced IFN-β synthesis in BMMCs in similar amounts as in bone marrow derived macrophages. IFN-β was expressed by mast cells in paws from naïve mice and during zymosan-induced inflammation. As described for macrophages the release of type I IFNs from mast cells depended on TLR internalization and endosome acidification. In conclusion, mast cells are able to produce several mediators including IFN-β, which are alone or in combination with each other able to regulate the phagocytotic activity of macrophages during resolution of inflammation.

scholarly journals Mast cells in collagen diseases

2019 ◽  
Vol 3 (2) ◽  
pp. 69
Author(s):  
Naoya Mikita ◽  
Yutaka Inaba ◽  
Takashi Yoshimasu ◽  
Nobuo Kanazawa ◽  
Fukumi Furukawa
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Mast Cells ◽  
Immune Cells ◽  
Lupus Erythematosus ◽  
Allergic Diseases ◽  
Local Inflammation ◽  
Systemic Lupus ◽  
Cytokines And Chemokines

Mast cells are involved in many immune reactions and diseases through 1) the expressions of several receptors, 2) productions of various mediators such as histamine, cytokines, and chemokines, 3) direct interactions with immune cells. Besides allergic diseases, mast cells have been also assumed to be involved in autoimmune diseases such as bullous pemphigoid, rheumatoid arthritis, and multiple sclerosis. Moreover, several studies reported the involvement of mast cells in collagen disease. In this article, we review recent findings about the role of mast cells especially in systemic lupus erythematosus and systemic sclerosis. In these diseases, mast cells seem to be involved in local inflammation and tissue damage partially in the targeted organ rather than the development of autoimmunity including production of autoantibodies.

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