scholarly journals Sesquiterpene-Loaded Co-Polymer Hybrid Nanoparticle Effects on Human Mast Cell Surface Receptor Expression, Granule Contents, and Degranulation

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 953
Author(s):  
Narcy Arizmendi ◽  
Hui Qian ◽  
Yiming Li ◽  
Marianna Kulka
Keyword(s):  
Mast Cell ◽  
Immunoglobulin E ◽  
Polymeric Nanoparticles ◽  
Synthesis Method ◽  
Allergic Inflammation ◽  
Receptor Expression ◽  
Cell Surface Receptor ◽  
Human Mast Cell ◽  
Cell Phenotype ◽  
Target Cells

Biodegradable polymeric nanoparticles (NPs) such as poly(lactic-co-glycolic acid) (PLGA) and polyvinyl alcohol (PVA) have been used as drug delivery systems for natural and synthetic compounds and are designed to control the loading and release of biodegradable materials to target cells, tissues, and organs. Eremophilane-type sesquiterpenes have anti-inflammatory properties but are lipophilic, cytotoxic, and not biocompatible with many cells. To determine whether biodegradable PLGA/PVA could improve the biocompatibility of sesquiterpenes, sesquiterpene-loaded NPs were synthesized and their effects on human mast cells (LAD2), the major effector cells of allergic inflammation, were determined. NPs composed of PLGA/PVA and two types of sesquiterpenes (fukinone, PLGA/PVA-21 and 10βH-8α,12-epidioxyeremophil-7(11)-en-8β-ol, PLGA/PVA-22) were produced using a microfluidic synthesis method. The NPs’ size distribution and morphology were evaluated by dynamic light scattering and cryogenic transmission electron microscopy (TEM). PLGA/PVA-21 and PLGA/PVA-22 were 60 to 70 nm and were readily internalized by LAD2 as shown by flow cytometry, fluorescence microscopy, and TEM. While unencapsulated sesquiterpenes decreased LAD2 cell viability by 20%, PLGA/PVA-21 and PLGA/PVA-22 did not alter LAD2 viability, showing that encapsulation improved the biocompatibility of the sesquiterpenes. PLGA/PVA-21 and PLGA/PVA-22 decreased the expression of genes encoding the subunits of the high affinity immunoglobulin E receptor (FcεR1α, FcεR1β, FcεR1γ) and the stem cell factor receptor (Kit,), suggesting that hybrid NPs could alter mast cell responses to antigens and shift their maturation. Similarly, PLGA/PVA-21 and PLGA/PVA-22 inhibited tryptase expression but had no effect on chymase expression, thereby promoting a shift to the tryptase-positive phenotype (MCT). Lastly, PLGA/PVA-21 and PLGA/PVA-22 inhibited mast cell degranulation when the LAD2 cells were activated by IgE crosslinking and FcεRI. Overall, our results suggest that PLGA/PVA-21 and PLGA/PVA-22 alter human mast cell phenotype and activation without modifying viability, making them a more biocompatible approach than treating cells with sesquiterpenes alone.

scholarly journals Divergent effects of acute and prolonged interleukin 33 exposure on mast cell IgE-mediated functions

2018 ◽  
Author(s):  
Elin Rönnberg ◽  
Avan Ghaib ◽  
Carlos Ceriol ◽  
Mattias Enoksson ◽  
Michel Arock ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Prolonged Exposure ◽  
Allergic Inflammation ◽  
Acute Effect ◽  
Receptor Expression ◽  
Human Mast Cell ◽  
Interleukin 33 ◽  
Cell Functions ◽  
Ige Mediated

AbstractBackgroundEpithelial cytokines, including IL-33 and TSLP, have attracted interest because of their roles in chronic allergic inflammation-related conditions such as asthma. Mast cells are one of the major targets of IL-33, to which they respond by secreting cytokines. Most studies performed thus far have investigated the acute effects of IL-33 on mast cells.ObjectiveThe objective of this study is to investigate how acute versus prolonged exposure of human mast cells to IL-33 and TSLP affects mediator synthesis and IgE-mediated activation.MethodsHuman lung mast cells (HLMCs), cord blood-derived mast cells (CBMCs), and the ROSA mast cell line were used for this study. Surface receptor expression and the levels of mediators were measured after treatment with IL-33 and/or TSLP.ResultsIL-33 induced the acute release of cytokines. Prolonged exposure to IL-33 increased while TSLP reduced intracellular levels of tryptase. Acute IL-33 treatment strongly potentiated IgE-mediated activation. In contrast, four days of exposure to IL-33 decreased IgE-mediated activation, an effect that was accompanied by a reduction in FcεRI expression.Conclusion & Clinical RelevanceWe show that IL-33 plays dual roles for mast cell functions. The acute effect includes cytokine release and the potentiation of IgE-mediated degranulation, whereas prolonged exposure to IL-33 reduces IgE-mediated activation. We conclude that mast cells act quickly in response to the alarmin IL-33 to initiate an acute inflammatory response, whereas extended exposure to IL-33 during prolonged inflammation reduces IgE-mediated responses. This negative feedback effect suggests the presence of a novel IL-33 mediated regulatory pathway that modulates IgE-induced human mast cell responses.

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

2018 ◽  
Vol 19 (12) ◽  
pp. 4092 ◽  
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.

Retinoic acid is a negative regulator for the differentiation of cord blood-derived human mast cell progenitors

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2821-2828 ◽  
Author(s):  
Tatsuya Kinoshita ◽  
Kenichi Koike ◽  
Hadija Hemed Mwamtemi ◽  
Susumu Ito ◽  
Shuichi Ishida ◽  
...  
Keyword(s):  
Mast Cell ◽  
Retinoic Acid ◽  
Mast Cells ◽  
Cord Blood ◽  
Cell Development ◽  
Negative Regulator ◽  
Human Mast Cell ◽  
Target Cells ◽  
Dependent Manner ◽  
Selective Agonist

We examined the effects of retinoids on the human mast cell development using a serum-deprived culture system. When 10-week cultured mast cells derived from CD34+ cord blood cells were used as target cells, both all-trans retinoic acid (ATRA) and 9-cis RA inhibited the progeny generation under stimulation with stem cell factor (SCF) in a dose-dependent manner (the number of progeny grown by SCF plus RA at 10−7 mol/L was one tenth of the value obtained by SCF alone). The early steps in mast cell development appear to be less sensitive to RA according to the single CD34+c-kit+ cord blood cell culture study. The optimal concentration of RAs also reduced the histamine concentration in the cultured mast cells (3.00 ± 0.47 pg per cell in SCF alone, 1.44 ± 0.18 pg per cell in SCF+ATRA, and 1.41 ± 0.10 pg per cell in SCF+9-cis RA). RT-PCR analyses showed the expression of RAR, RARβ, RXR, and RXRβ messenger ribonucleic acid (mRNA) in 10-week cultured mast cells. The addition of an RAR-selective agonist at 10−10 mol/L to 10−7 mol/L decreased the number of mast cells grown in SCF, whereas an RXR-selective agonist at up to 10−8 mol/L was inactive. Among RAR subtype selective retinoids used at 10−9 mol/L to 10−7 mol/L, only the RAR agonist was equivalent to ATRA at 10−7 mol/L in its ability to inhibit mast cell growth. Conversely, the addition of excess concentrations of a RAR antagonist profoundly counteracted the retinoid-mediated suppressive effects. These results suggest that RA inhibits SCF-dependent differentiation of human mast cell progenitors through a specific receptor.

Aqueous Extract of Mosla chinensis Inhibits Mast Cell-Mediated Allergic Inflammation

2012 ◽  
Vol 40 (06) ◽  
pp. 1257-1270 ◽  
Author(s):  
Hui-Hun Kim ◽  
Jin-Su Yoo ◽  
Tae-Yong Shin ◽  
Sang-Hyun Kim
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Histamine Release ◽  
Aqueous Extract ◽  
Proinflammatory Cytokines ◽  
Immunoglobulin E ◽  
Inflammatory Diseases ◽  
Allergic Inflammation ◽  
Inhibitory Effect ◽  
Ige Mediated

Allergic inflammatory diseases such as food allergy, asthma, sinusitis, and atopic dermatitis are increasing worldwide. In this study, we investigated the effects of aqueous extract of Mosla chinensis Max. (AMC) on mast cell-mediated allergic inflammation and studied the possible mechanism of this action. AMC inhibited compound 48/80-induced systemic and immunoglobulin E (IgE)-mediated local anaphylaxis. AMC reduced intracellular calcium levels and downstream histamine release from rat peritoneal mast cells activated by compound 48/80 or IgE. In addition, AMC decreased gene expression and secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8 in human mast cells. The inhibitory effect of AMC on cytokine expression was nuclear factor (NF)-κB dependent. Our results indicate that AMC inhibits mast cell-mediated allergic inflammatory reaction by suppressing histamine release and expression of proinflammatory cytokines and the involvement of calcium and NF-κB in these effects. AMC might be a possible therapeutic candidate for allergic inflammatory disorders.

scholarly journals Roles of IgE and Histamine in Mast Cell Maturation

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2170
Author(s):  
Satoshi Tanaka ◽  
Kazuyuki Furuta
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Immunoglobulin E ◽  
Cell Maturation ◽  
Tissue Type ◽  
Human Mast Cell ◽  
Therapeutic Effects ◽  
Serum Ige ◽  
Cell Functions ◽  
Histamine Synthesis

Mast cells are activated upon immunoglobulin E (IgE)-mediated antigen stimulation, and release a wide variety of mediators, including histamine to trigger inflammatory responses. The surface expression levels of Fcε receptor I (FcεRI), a high affinity receptor of IgE, were found to be positively regulated by IgE. IgE could protect murine cultured mast cells from apoptotic cell death induced by the deprivation of interleukin-3 and a certain kind of IgE could activate immature mast cells in the absence of antigens, leading to the release of pro-inflammatory cytokines and a transient increase in histamine synthesis. Histamine synthesis in mast cells was found to be required for the maturation of murine connective tissue-type mast cells, raising the possibility that IgE indirectly modulates local mast cell maturation. Although it remains controversial to what extent this concept of “monomeric IgE effects” could have relevance in the modulation of human mast cell functions, the therapeutic effects of anti-IgE antibodies might be accounted for in terms of the decreased serum IgE concentrations. Because drastic increases in serum IgE concentrations are often observed in patients with atopic dermatitis and chronic urticaria, a close investigation of the roles of IgE in mast cell maturation should contribute to development of novel therapeutic approaches for these inflammatory diseases.

scholarly journals The Adaptor 3BP2 Is Required for KIT Receptor Expression and Human Mast Cell Survival

2015 ◽  
Vol 194 (9) ◽  
pp. 4309-4318 ◽  
Author(s):  
Erola Ainsua-Enrich ◽  
Eva Serrano-Candelas ◽  
Damiana Álvarez-Errico ◽  
César Picado ◽  
Joan Sayós ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Survival ◽  
Receptor Expression ◽  
Human Mast Cell ◽  
Kit Receptor

Effects of IL-4 and IL-13 on adenosine receptor expression and responsiveness of the human mast cell line 1

2008 ◽  
Vol 8 (6) ◽  
pp. 866-873 ◽  
Author(s):  
Mieke Versluis ◽  
Dirkje S. Postma ◽  
Wim Timens ◽  
Machteld N. Hylkema
Keyword(s):  
Mast Cell ◽  
Cell Line ◽  
Adenosine Receptor ◽  
Receptor Expression ◽  
Human Mast Cell ◽  
Mast Cell Line

scholarly journals Correction: The Adaptor 3BP2 Is Required for KIT Receptor Expression and Human Mast Cell Survival

2017 ◽  
Vol 200 (3) ◽  
pp. 1227-1227
Author(s):  
Erola Ainsua-Enrich ◽  
Eva Serrano-Candelas ◽  
Damiana Álvarez-Errico ◽  
César Picado ◽  
Joan Sayós ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Survival ◽  
Receptor Expression ◽  
Human Mast Cell ◽  
Kit Receptor

Role of protein phosphatases in the regulation of human mast cell and basophil function

1999 ◽  
Vol 277 (6) ◽  
pp. C1021-C1028 ◽  
Author(s):  
Matthew J. Peirce ◽  
Michael R. Munday ◽  
Peter T. Peachell
Keyword(s):  
Mast Cell ◽  
Protein Kinases ◽  
Inflammatory Diseases ◽  
Protein Phosphatases ◽  
Human Mast Cell ◽  
Target Cells ◽  
Intact Cells ◽  
Phosphatase Inhibitors ◽  
Extracellular Stimuli

Many extracellular stimuli mediate physiological change in target cells by altering the phosphorylation state of proteins. These alterations result from the dynamic interplay of protein kinases, which mediate phosphorylations, and protein phosphatases, which catalyse dephosphorylations. The antigen-mediated aggregation of high-affinity receptors for IgE on mast cells and basophils triggers rapid changes in the phosphorylation of many proteins and culminates in the generation of inflammatory mediators involved in allergic inflammatory diseases such as asthma. Although protein kinases have an established role in this process, less is known about the involvement of protein phosphatases. This imbalance has been redressed in recent years by the availability of phosphatase inhibitors, such as okadaic acid, that facilitate investigations of the role of protein phosphatases in intact cells. Here we review a number of studies in which inhibitors of protein phosphatases have been used to shed light on the potential importance of these enzymes in the regulation of human mast cell and human basophil function.

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