scholarly journals Metformin inhibits IgE‐ and aryl hydrocarbon receptor‐mediated mast cell activation in vitro and in vivo

2018 ◽  
Vol 48 (12) ◽  
pp. 1989-1996 ◽  
Author(s):  
Hsueh‐Chun Wang ◽  
Shau‐Ku Huang
Keyword(s):  
Mast Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Aryl Hydrocarbon

scholarly journals Increased Severity of Local and Systemic Anaphylactic Reactions in Gp49b1-Deficient Mice

2001 ◽  
Vol 194 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Massoud Daheshia ◽  
Daniel S. Friend ◽  
Michael J. Grusby ◽  
K. Frank Austen ◽  
Howard R. Katz
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Critical Question ◽  
Increased Sensitivity ◽  
Antibody Levels ◽  
Deficient Mice

gp49B1 is an immunoglobulin (Ig) superfamily member that inhibits FcεRI-induced mast cell activation when the two receptors are coligated with antibodies in vitro. The critical question of in vivo function of gp49B1 is now addressed in gene-disrupted mice. gp49B1-deficient mice exhibited a significantly increased sensitivity to IgE-dependent passive cutaneous anaphylaxis as assessed by greater tissue swelling and mast cell degranulation in situ. Importantly, by the same criteria, the absence of gp49B1 also resulted in a lower threshold for antigen challenge in active cutaneous anaphylaxis, in which the antigen-specific antibody levels were comparable in gp49B1-deficient and sufficient mice. Moreover, the absence of gp49B1 resulted in a significantly greater and faster death rate in active systemic anaphylaxis. These results indicate that gp49B1 innately dampens adaptive immediate hypersensitivity responses by suppressing mast cell activation in vivo. In addition, this study provides a new concept and target for regulation of allergic disease susceptibility and severity.

scholarly journals IgE Enhances Mouse Mast Cell FcεRI Expression In Vitro and In Vivo: Evidence for a Novel Amplification Mechanism in IgE-dependent Reactions

1997 ◽  
Vol 185 (4) ◽  
pp. 663-672 ◽  
Author(s):  
Masao Yamaguchi ◽  
Chris S. Lantz ◽  
Hans C. Oettgen ◽  
Ildy M. Katona ◽  
Tony Fleming ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Specific Antigen ◽  
Mast Cell Activation ◽  
Proinflammatory Mediators ◽  
Mouse Mast Cell

The binding of immunoglobulin E (IgE) to high affinity IgE receptors (FcεRI) expressed on the surface of mast cells primes these cells to secrete, upon subsequent exposure to specific antigen, a panel of proinflammatory mediators, which includes cytokines that can also have immunoregulatory activities. This IgE- and antigen-specific mast cell activation and mediator production is thought to be critical to the pathogenesis of allergic disorders, such as anaphylaxis and asthma, and also contributes to host defense against parasites. We now report that exposure to IgE results in a striking (up to 32-fold) upregulation of surface expression of FcεRI on mouse mast cells in vitro or in vivo. Moreover, baseline levels of FcεRI expression on peritoneal mast cells from genetically IgE-deficient (IgE −/−) mice are dramatically reduced (by ∼83%) compared with those on cells from the corresponding normal mice. In vitro studies indicate that the IgE-dependent upregulation of mouse mast cell FcεRI expression has two components: an early cycloheximide-insensitive phase, followed by a later and more sustained component that is highly sensitive to inhibition by cycloheximide. In turn, IgE-dependent upregulation of FcεRI expression significantly enhances the ability of mouse mast cells to release serotonin, interleukin-6 (IL-6), and IL-4 in response to challenge with IgE and specific antigen. The demonstration that IgE-dependent enhancement of mast cell FcεRI expression permits mast cells to respond to antigen challenge with increased production of proinflammatory and immunoregulatory mediators provides new insights into both the pathogenesis of allergic diseases and the regulation of protective host responses to parasites.

A tryptophan metabolite, kynurenine, promotes mast cell activation through aryl hydrocarbon receptor

Allergy ◽  
2014 ◽  
Vol 69 (4) ◽  
pp. 445-452 ◽  
Author(s):  
H. Kawasaki ◽  
H.-W. Chang ◽  
H.-C. Tseng ◽  
S.-C. Hsu ◽  
S.-J. Yang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Aryl Hydrocarbon Receptor ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Aryl Hydrocarbon ◽  
Tryptophan Metabolite

scholarly journals Miltefosine Inhibits Human Mast Cell Activation and Mediator Release Both In Vitro and In Vivo

2009 ◽  
Vol 129 (2) ◽  
pp. 496-498 ◽  
Author(s):  
Karsten Weller ◽  
Metin Artuc ◽  
Gary Jennings ◽  
Tim Friedrichson ◽  
Sven Guhl ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Mediator Release ◽  
Mast Cell Activation ◽  
Human Mast Cell

scholarly journals Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo

2020 ◽  
Vol 177 (12) ◽  
pp. 2848-2859
Author(s):  
Li‐Na Zhang ◽  
Kunmei Ji ◽  
Yue‐Tong Sun ◽  
Yi‐Bo Hou ◽  
Jia‐Jie Chen
Keyword(s):  
Mast Cell ◽  
Cell Activation ◽  
Kinase Inhibitor ◽  
Aurora Kinase ◽  
Mast Cell Activation ◽  
Aurora Kinase Inhibitor

scholarly journals S100A4 Is Critical for a Mouse Model of Allergic Asthma by Impacting Mast Cell Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Tongqian Wu ◽  
Lan Ma ◽  
Xiaoqian Jin ◽  
Jingjing He ◽  
Ke Chen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Calcium Binding ◽  
Cell Activation ◽  
Allergic Diseases ◽  
Lavage Fluid ◽  
Mast Cell Activation ◽  
Asthma Model

BackgroundThe calcium-binding protein S100A4 demonstrates important regulatory roles in many biological processes including tumorigenesis and inflammatory disorders such as allergy. However, the specific mechanism of the contribution of S100A4 to allergic diseases awaits further clarification.ObjectiveTo address the effect of S100A4 on the regulation of mast cell activation and its impact on allergy.MethodsBone marrow-derived cultured mast cells (BMMCs) were derived from wild-type (WT) or S100A4-/- mice for in vitro investigation. WT and S100A4-/- mice were induced to develop a passive cutaneous anaphylaxis (PCA) model, a passive systemic anaphylaxis (PSA) model, and an ovalbumin (OVA)-mediated mouse asthma model.ResultsFollowing OVA/alum-based sensitization and provocation, S100A4-/- mice demonstrated overall suppressed levels of serum anti-OVA IgE and IgG antibodies and proinflammatory cytokines in serum, bronchoalveolar lavage fluid (BALF), and lung exudates. S100A4-/- mice exhibited less severe asthma signs which included inflammatory cell infiltration in the lung tissue and BALF, and suppressed mast cell recruitment in the lungs. Reduced levels of antigen reencounter-induced splenocyte proliferation in vitro were recorded in splenocytes from OVA-sensitized and challenged mice that lacked S100A4-/-. Furthermore, deficiency in the S100A4 gene could dampen mast cell activation both in vitro and in vivo, evidenced by reduced β-hexosaminidase release and compromised PCA and PSA reaction. We also provided evidence supporting the expression of S100A4 by mast cells.ConclusionS100A4 is required for mast cell functional activation, and S100A4 may participate in the regulation of allergic responses at least partly through regulating the activation of mast cells.

Abstract 1947: Chymase Inhibition Reduces the Incidence of Intraplaque Hemorrhage and Induces a Stable Atherosclerotic Plaque Phenotype in ApoE Deficient Mice

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ilze Bot ◽  
Marijke M Westra ◽  
Sandra H van Heiningen ◽  
Hans Hilpert ◽  
Inge M Lankhuizen ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Atherosclerotic Plaque ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Intraplaque Hemorrhage ◽  
Plaque Stability ◽  
Plaque Destabilization

Mast cells are abundantly present in perivascular tissue during atherosclerotic plaque progression and were previously demonstrated to contribute significantly to plaque destabilization. In this study, we aimed to investigate to what extent inhibition of chymase, one of the mast cell proteases, could enhance plaque stability. We demonstrated earlier that the specific chymase inhibitor RO501 (1 μM) was able to quench mast cell activation in vitro , as illustrated by a decreased β-hexosaminidase (−41% and −80%, respectively; P<0.05) as well as chymase activity in the releasate of activated MC/9 and peritoneal mast cells (−71% and −65%, respectively; P<0.05). Next, we assessed whether chymase inhibition was also effective in vivo. Atherosclerotic carotid artery lesions were induced in ApoE −/− mice by perivascular collar placement and mast cells were activated by DNP challenge systemically during lesion development. RO501 (50 mg/kg/day) was administered as diet supplement, leading to serum concentrations of ~2 μM. While plaque size after 6 weeks of treatment did not differ, collagen content of the lesions was 2-fold enhanced in mice treated with RO501 compared to controls (1.4 ± 0.5% and 0.7 ± 0.2%, respectively). This was accompanied by a significant decrease in necrotic core size of the plaques (controls: 52 ± 3% versus RO501: 41 ± 4%, P<0.05). To determine the effects of chymase inhibition after acute mast cell activation in advanced plaques, perivascular mast cells were focally activated in the adventitia of advanced lesions in ApoE −/− mice, which were treated with RO501 as described above. At three days after focal mast cell challenge, the incidence of intraplaque hemorrhage (IPH) was inhibited from 23% in control mice to 4.5% in RO501 treated mice, while also the plaque erythrocyte area was reduced by >90% from 1.2 ± 0.6*10 3 to 0.1 ± 0.08*10 3 μm 2 (P<0.05). Also, we observed a reduction in apoptotic cells (RO501: 0.68 ± 0.20% vs. 1.01 ± 0.36% for IPH negative controls and 1.23 ± 0.42% for IPH + plaques). In conclusion, our data suggest that chymase inhibition at least partly prevents the detrimental effects of perivascular mast cells on plaque stability, identifying chymase inhibition as a new therapeutic approach in the prevention of acute coronary syndromes.

scholarly journals SWAP-70 Regulates c-kit-Induced Mast Cell Activation, Cell-Cell Adhesion, and Migration

2004 ◽  
Vol 24 (23) ◽  
pp. 10277-10288 ◽  
Author(s):  
Raja Rajeswari Sivalenka ◽  
Rolf Jessberger
Keyword(s):  
Mast Cell ◽  
Cell Adhesion ◽  
Mast Cells ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Calcium Flux ◽  
Mutant Cells

ABSTRACT SWAP-70, an unusual phosphatidylinositol-3-kinase-dependent protein that interacts with the RhoGTPase Rac, is highly expressed in mast cells. Cultured bone marrow mast cells (BMMC) from SWAP-70−/− mice are reduced in FcεRI-triggered degranulation. This report describes the hitherto-unknown role of SWAP-70 in c-kit receptor signaling, a key proliferation and differentiation pathway in mast cells. Consistent with the role of Rac in cell motility and regulation of the actin cytoskeleton, mutant cells show abnormal actin rearrangements and are deficient in migration in vitro and in vivo. SWAP-70−/− BMMC are impaired in calcium flux, in proper translocation and activity of Akt kinase (required for mast cell activation and survival), and in translocation of Rac1 and Rac2 upon c-kit stimulation. Adhesion to fibronectin is reduced, but homotypic cell association induced through c-kit is strongly increased in SWAP-70−/− BMMC. Homotypic association requires extracellular Ca2+ and depends on the integrin αLβ2 (LFA-1). ERK is hyperactivated upon c-kit signaling in adherent and dispersed mutant cells. Together, we suggest that SWAP-70 is an important regulator of specific effector pathways in c-kit signaling, including mast cell activation, migration, and cell adhesion.

scholarly journals Sinomenine potentiates P815 cell degranulation via upregulation of Ca2+ mobilization through the Lyn/PLCγ/IP3R pathway

2016 ◽  
Vol 29 (4) ◽  
pp. 676-683 ◽  
Author(s):  
Nan Wang ◽  
Rui Liu ◽  
Yanping Liu ◽  
Ruirui Zhang ◽  
Langchong He
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Drug Allergy ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sinomenium Acutum ◽  
Underlying Mechanisms

Mast cells are vital mediators of drug allergy and, therefore, studying the relationship between drug allergy and mast cells is essential. Sinomenine is the principal active component of Sinomenium acutum, which has anti-inflammatory and anti-immune effects, and is used to treat various rheumatoid diseases. However, allergic responses to sinomenine are frequently reported. Therefore, this study assessed the effects of sinomenine on mast cell activation to characterize its allergic effects and the underlying mechanisms. Enzyme-linked immunosorbent assay (ELISA), western blot analyses, and degranulation assays were performed to measure pro-inflammatory and allergic mediators in P815 cells. The allergenic effects of sinomenine were also determined in mice by using active general anaphylaxis (ASA). The results indicated that sinomenine induced inositol-1,4,5-trisphosphate (IP3) production and the release of histamine, interleukin (IL)-6, and endoplasmic reticulum Ca2+ in P815 cells. Furthermore, sinomenine upregulated the phosphorylation of sarcoma (Src), phospholipase C (PLC)-γ1, and IP3 receptor (R). Therefore, sinomenine induced concentration-dependent mast cell activation directly in vitro. Furthermore, our in vivo data identified an appropriate intravenous dose that did not induce these allergic effects, thereby providing information for the potential safe clinical use of sinomenine.

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