scholarly journals Borrelia burgdorferiSpirochetes Induce Mast Cell Activation and Cytokine Release

1999 ◽  
Vol 67 (3) ◽  
pp. 1107-1115 ◽  
Author(s):  
Jeffrey Talkington ◽  
Steven P. Nickell
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Cell Types ◽  
Host Cells ◽  
Mast Cell Activation ◽  
Cytokine Release ◽  
Necrosis Factor Alpha ◽  
Tnf Α

ABSTRACT The Lyme disease spirochete, Borrelia burgdorferi, is introduced into human hosts via tick bites. Among the cell types present in the skin which may initially contact spirochetes are mast cells. Since spirochetes are known to activate a variety of cell types in vitro, we tested whether B. burgdorferi spirochetes could activate mast cells. We report here that freshly isolated rat peritoneal mast cells or mouse MC/9 mast cells cultured in vitro with live or freeze-thawed B. burgdorferi spirochetes undergo low but detectable degranulation, as measured by [5-3H] hydroxytryptamine release, and they synthesize and secrete the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). In contrast to findings in previous studies, where B. burgdorferi-associated activity was shown to be dependent upon protein lipidation, mast cell TNF-α release was not induced by either lipidated or unlipidated recombinant OspA. This activity was additionally shown to be protease sensitive and surface expressed. Finally, comparisons of TNF-α-inducing activity in known low-, intermediate-, and high-passage B. burgdorferi B31 isolates demonstrated passage-dependent loss of activity, indicating that the activity is probably plasmid encoded. These findings document the presence in low-passage B. burgdorferi spirochetes of a novel lipidation-independent activity capable of inducing cytokine release from host cells.

SELE Downregulation Suppresses Mast Cell Accumulation to Protect against Inflammatory Response in Chronic Idiopathic Urticaria

2020 ◽  
pp. 1-11
Author(s):  
Hong Wang ◽  
Yangchun Xu ◽  
Meishan Jin ◽  
Wen Yuan
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Chronic Idiopathic Urticaria ◽  
Mast Cell Activation ◽  
Clinical Samples ◽  
Inflammatory Factor ◽  
Tnf Α ◽  
Elevated Expression

<b><i>Background:</i></b><i></i>Chronic idiopathic urticaria (CIU) represents a common skin disorder often characterized by mast cell activation and secretion of histamine and other proinflammatory factors. E-selectin (SELE) has been implicated in the pathogenesis of common inflammatory cutaneous disorders, while the role of SELE in CIU is yet to be fully understood. Thus, we aimed to investigate the mechanism by which SELE influences CIU in connection with the involvement of mast cells. <b><i>Methods:</i></b> SELE expression was measured in blood samples obtained from CIU patients and normal individuals. A CIU mouse model was subsequently established by intradermally injecting a normal saline solution with ovalbumin IgE antiserum into the mice. Loss- and gain-of-function investigations were conducted on the mouse models. The number of degranulated mast cells and the amount of histamine release in vitro were determined. The levels of SELE, tumor necrosis factor (TNF)-α, homologous restriction factor (HRF), and interleukin (IL)-6 levels were determined. <b><i>Results:</i></b> The CIU clinical samples exhibited upregulated SELE, while the CIU mice showed increased mast cell degranulation and an increased rate of histamine directional release, as well as an elevated expression of SELE, TNF-α, HRF, and IL-6. SELE silencing was found to decrease the number of degranulated mast cells and reduce the rate of histamine directional release, along with suppressed TNF-α, HRF, and IL-6 expression, in the serum of CIU mice. Ketotifen was observed to rescue the increased expression of TNF-α, HRF, and IL-6 caused by SELE overexpression. <b><i>Conclusions:</i></b><i></i>This study highlights the potential of SELE downregulation to repress inflammatory factor secretion caused by the accumulation of mast cells, which ultimately inhibits the development of CIU.

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.

Abstract 459: Vascular Neuropeptide Y Contributes to Atherosclerotic Plaque Progression and Perivascular Mast Cell Activation

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
H Maxime Lagraauw ◽  
Marijke M Westra ◽  
Martine Bot ◽  
Anouk Wezel ◽  
Peter J Santbrink ◽  
...  
Keyword(s):  
Mast Cell ◽  
Neuropeptide Y ◽  
Atherosclerotic Plaque ◽  
Cell Activation ◽  
Lentiviral Vector ◽  
Cell Types ◽  
Mast Cell Activation ◽  
Plaque Progression ◽  
Plaque Development

Aim: Neuropeptide Y is an abundantly expressed neurotransmitter capable of modulating both immune and metabolic responses related to the development of atherosclerosis. NPY receptors are expressed by a number of vascular wall cell types, among which mast cells. However, the direct effects of NPY on perivascular inflammation and atherosclerotic plaque progression remain to be investigated. In this study we thus aimed to determine whether NPY is expressed in atherosclerotic plaques and to establish its role in atherosclerotic plaque development. Methods and Results: NPY expression was seen to be increased up to 2-fold in unstable human endarterectomy plaques, as compared to stable plaques (p<0.05, n=9-12), and to be significantly upregulated during lesion progression in apoE -/- mice (p<0.001, n=4 per timepoint). In apoE -/- mice overexpression of NPY in the carotid artery by means of local application of a lentiviral vector significantly increased atherosclerotic plaque size compared to controls (54 ± 9 *10 3 μm 2 versus 31 ± 6 *10 3 μm 2 , P<0.05, n=12), while plaque composition was unaffected. Interestingly, perivascular mast cell activation was significantly higher in the NPY-overexpressing mice (48.1 ± 4.0 % versus 30.2 ± 6.0 %, P<0.05), suggesting that NPY may impact plaque progression in part via mast cell activation. Furthermore, in vitro NPY-induced murine mast cell activation resulted in the release of pro-atherogenic mediators including IL-6 (515.0 ± 12.5 pg/ml vs. 87.5 ± 5.0 pg/ml) and tryptase. Conclusions: Our data show that NPY expression is increased during atherogenesis and in particular in unstable plaques. Furthermore, perivascular overexpression of NPY promoted plaque development and perivascular mast cell activation, suggestive of a role for NPY-induced mast cell activation in lesion progression.

Abstract 476: Mast Cell--Mediated Neutrophil Influx Enhances Plaque Progression

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Anouk Wezel ◽  
H Maxime Lagraauw ◽  
Daniël van der Velden ◽  
Saskia C de Jager ◽  
Paul H Quax ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Neutrophil Migration ◽  
Fold Increase ◽  
Mast Cell Activation ◽  
Neutrophil Influx ◽  
Migration Assay ◽  
Cell Activator

Rationale: Activated mast cells have been identified in atherosclerotic plaques. As mast cells have the ability to release chemokines that mediate leukocyte fluxes, we propose that activated mast cells play a pivotal role in leukocyte recruitment during atherosclerosis. Methods and Results: Diet fed B-cell deficient apoE-/-muChain mice, which lack endogenous IgE, received 6 IgE or PBS injections over a period of 8 weeks. Mast cells in the aortic root were significantly more activated after IgE treatment and concomitantly, we detected an increase in plaque size (P=0.050). Intriguingly, a striking increase in the amount of perivascular neutrophils was observed in IgE treated mice (control: 57.6 ± 10.6 neutrophils/mm2 tissue; IgE: 183.0 ± 38.7 neutrophils/mm2 tissue; P=0.01). In order to investigate if activated mast cells can directly attract neutrophils, we injected C57Bl/6 or mast cell deficient Kit(W-sh/W-sh) mice intra-peritoneal with the mast cell activator 48/80. Interestingly, mast cell activation led to a massive neutrophil influx into the peritoneal cavity, while neutrophil numbers in mast cell deficient mice remained unaffected. To confirm these findings, we performed an in vitro migration assay. Indeed, supernatant of activated mast cells caused a 3-fold increase in neutrophil migration (P=0.007). Moreover, addition of anti-CXCR2 to the neutrophils resulted in a major reduction of migration (P=0.03) whereas anti-CXCR4 did not reduce migration significantly. Conclusions: Chemokines released from activated perivascular mast cells induce neutrophil recruitment to the atherosclerotic plaque, thereby aggravating the inflammatory response.

scholarly journals Anaplasma phagocytophilum Infects Mast Cells via α1,3-Fucosylated but Not Sialylated Glycans and Inhibits IgE-Mediated Cytokine Production and Histamine Release

2011 ◽  
Vol 79 (7) ◽  
pp. 2717-2726 ◽  
Author(s):  
Nore Ojogun ◽  
Brian Barnstein ◽  
Bernice Huang ◽  
Carole A. Oskeritzian ◽  
Jonathon W. Homeister ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Anaplasma Phagocytophilum ◽  
Defense Mechanisms ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Murine Bone Marrow ◽  
Granulocytic Anaplasmosis

ABSTRACTMast cells are sentinels for infection. Upon exposure to pathogens, they release their stores of proinflammatory cytokines, chemokines, and histamine. Mast cells are also important for the control of certain tick-borne infections.Anaplasma phagocytophilumis an obligate intracellular tick-transmitted bacterium that infects neutrophils to cause the emerging disease granulocytic anaplasmosis.A. phagocytophilumadhesion to and infection of neutrophils depend on sialylated and α1,3-fucosylated glycans. We investigated the hypotheses thatA. phagocytophiluminvades mast cells and inhibits mast cell activation. We demonstrate thatA. phagocytophilumbinds and/or infects murine bone marrow-derived mast cells (BMMCs), murine peritoneal mast cells, and human skin-derived mast cells.A. phagocytophiluminfection of BMMCs depends on α1,3-fucosylated, but not sialylated, glycans.A. phagocytophilumbinding to and invasion of BMMCs do not elicit proinflammatory cytokine secretion. Moreover,A. phagocytophilum-infected cells are inhibited in the release of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-13, and histamine following stimulation with IgE or antigen. Thus,A. phagocytophilummitigates mast cell activation. These findings potentially represent a novel means by whichA. phagocytophilumusurps host defense mechanisms and shed light on the interplay between mast cells and vector-borne bacterial pathogens.

scholarly journals Rhubarb-Evoke Mucus Secretion through Aggregation and Degranulation of Mast Cell in the Colon of Rat: In vivo and ex vivo studies

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Di Wu ◽  
Xiaowei Xue ◽  
Chenchen Gao ◽  
Yuehong Liu ◽  
Tiantian Wang ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Water Content ◽  
Cell Activation ◽  
Ex Vivo ◽  
Mucus Secretion ◽  
Enteric Neurons ◽  
Mast Cell Activation ◽  
Rat Colon

AbstractRhubarb is commonly used to treat constipation in China for its function of promoting intestinal movement and optimum water content in feces. However, its mechanism of mucus secretion is vague. The aim of the study is to investigate the role of mast cells and enteric neurons in rhubarb extract (RE)-induced mucus secretion in the rat colon. Immunofluorescence was used to detect histamine receptors. Western blotting and 3,3′-diaminobenzidine (DAB) were applied to explore the content changes of mast cells activation. The changes in colonic goblet cells (GCs) were determined by means of PAS/AB staining. An intestinal perfusion system with a Bradford protein assay kit was directly to estimate in vitro secretion. And the cytokines were investigated with ELISA. The longitudinal aspect of this study indicate that the number and water content of faecal pellets were enhanced after the administration of different doses of RE accompanied by mast cells accumulated and increased the content of interferon (IFN) -γ or decreased the levels of interleukin (IL) −10 at doses of 3 and 6 g/kg. Pretreatment with ketotifen, mast cell stabilizer, had partially inhibited on RE-induced mucus secretion. Furthermore, RE induced the release of acetylcholine and mucin-2 in the colonic tissue and the histamine levels from the faeces. The results suggest that RE induced colonic mucus secretion involves mast cell activation and some cytokine.

scholarly journals Phospholipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells

Blood ◽  
2006 ◽  
Vol 108 (3) ◽  
pp. 956-964 ◽  
Author(s):  
Jun Ho Lee ◽  
Young Mi Kim ◽  
Nam Wook Kim ◽  
Jie Wan Kim ◽  
Erk Her ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Adaptor Proteins ◽  
Mast Cell Activation ◽  
Critical Event ◽  
Phospholipase D1 ◽  
Key Enzyme

Abstract Mast cells are responsible for IgE-mediated allergic reactions. Phospholipase D1 (PLD1) and PLD2 regulate mast cell activation, but the mechanisms remain unclear. Here we show that PLD2 associates with and promotes activation of Syk, a key enzyme in mast cell activation. Antigen stimulation resulted in increased association and colocalization of Syk with PLD2 on the plasma membrane as indicated by coimmunoprecipitation and confocal microscopy. This association was dependent on tyrosine phosphorylation of Syk but not on PLD2 activity. In vitro, PLD2 interacted via its Phox homology (PX) domain with recombinant Syk to induce phosphorylation and activation of Syk. Furthermore, overexpression of PLD2 or catalytically inactive PLD2K758R enhanced antigen-induced phosphorylations of Syk and its downstream targets, the adaptor proteins LAT and SLP-76, while expression of a PLD2 siRNA blocked these phosphorylations. Apparently, the interaction of PLD2 with Syk is an early critical event in the activation of mast cells.

Spiraeoside inhibits mast cells activation and IgE-mediated allergic responses by suppressing phospholipase C-γ-mediated signaling

2015 ◽  
Vol 93 (3) ◽  
pp. 227-235 ◽  
Author(s):  
Jung Kuk Kim ◽  
Young-Kyo Seo ◽  
Sehoon Park ◽  
Soo-Ah Park ◽  
Seyoung Lim ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Phospholipase C ◽  
Cell Activation ◽  
Mapk Signaling ◽  
Mast Cell Activation ◽  
Tnf Α ◽  
Ige Mediated ◽  
Subsequent Activation

Mast cells are responsible for IgE-mediated allergic responses through the secretion of various inflammatory cytokines and mediators. Therefore, the pharmacological regulation of mast cell activation is an important goal in the development of novel anti-allergic drugs. In this study, we found that spiraeoside (SP) inhibits mast cell activation and allergic responses in vivo. SP dose-dependently inhibited the degranulation induced by IgE-antigen (Ag) stimulation in RBL-2H3 mast cells without cytotoxic effects. At the molecular level, SP reduced the Ag-induced phosphorylation and subsequent activation of phospholipase C-γ2 (PLC-γ2). Moreover, SP inhibited the phosphorylation of spleen tyrosine kinase (Syk), linker for activation of T cells (LAT), and downstream MAPKs, such as ERK1/2, p38, and JNK, eventually attenuating expression of TNF-α and IL-4. Finally, we found that SP significantly inhibited IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Taken together, our results strongly suggest that SP suppresses IgE-mediated mast cell activation and allergic responses by inhibiting Lyn-induced PLC-γ2/MAPK signaling in mast cells.

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.

scholarly journals Chymase released from hypoxia-activated cardiac mast cells cleaves human apoA-I at Tyr192 and compromises its cardioprotective activity

2018 ◽  
Vol 59 (6) ◽  
pp. 945-957 ◽  
Author(s):  
Ilona Kareinen ◽  
Marc Baumann ◽  
Su Duy Nguyen ◽  
Katariina Maaninka ◽  
Andrey Anisimov ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Low Flow ◽  
Human Coronary Artery ◽  
Functional Protein ◽  
Rat Hearts ◽  
Highly Sensitive

ApoA-I, the main structural and functional protein of HDL particles, is cardioprotective, but also highly sensitive to proteolytic cleavage. Here, we investigated the effect of cardiac mast cell activation and ensuing chymase secretion on apoA-I degradation using isolated rat hearts in the Langendorff perfusion system. Cardiac mast cells were activated by injection of compound 48/80 into the coronary circulation or by low-flow myocardial ischemia, after which lipid-free apoA-I was injected and collected in the coronary effluent for cleavage analysis. Mast cell activation by 48/80 resulted in apoA-I cleavage at sites Tyr192 and Phe229, but hypoxic activation at Tyr192 only. In vitro, the proteolytic end-product of apoA-I with either rat or human chymase was the Tyr192-truncated fragment. This fragment, when compared with intact apoA-I, showed reduced ability to promote migration of cultured human coronary artery endothelial cells in a wound-healing assay. We propose that C-terminal truncation of apoA-I by chymase released from cardiac mast cells during ischemia impairs the ability of apoA-I to heal damaged endothelium in the ischemic myocardium.

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