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Mast Cell Activation (mast + cell_activation)
Selected AbstractsPersistent Linear Bands in Infancy Acquired After Local Pressure: A Consequence of Mast Cell Activation?PEDIATRIC DERMATOLOGY, Issue 4 2007Lara S Ford B.Sc., M.B.B.S. We speculate that release of mast cell mediators associated with the dermographism may have triggered the development of the linear bands. [source] Mast cell activation after adenosine inhalation challenge in patients with bronchial asthmaALLERGY, Issue 1 2008G. Bochenek No abstract is available for this article. [source] Airway smooth muscle proliferation and survival is not modulated by mast cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 2 2010D. Kaur Summary Background Airway smooth muscle (ASM) hyperplasia and mast cell localization within the ASM bundle are important features of asthma. The cause of this increased ASM mass is uncertain and whether it is a consequence of ASM,mast cell interactions is unknown. Objective We sought to investigate ASM proliferation and survival in asthma and the effects of co-culture with mast cells. Methods Primary ASM cultures were derived from 11 subjects with asthma and 12 non-asthmatic controls. ASM cells were cultured for up to 10 days in the presence or absence of serum either alone or in co-culture with the human mast cell line-1, unstimulated human lung mast cells (HLMC) or IgE/anti-IgE-activated HLMC. Proliferation was assessed by cell counts, CFSE assay and thymidine incorporation. Apoptosis and necrosis were analysed by Annexin V/propidium iodide staining using flow cytometry and by assessment of nuclear morphology using immunofluorescence. Mast cell activation was confirmed by the measurement of histamine release. Results Using a number of techniques, we found that ASM proliferation and survival was not significantly different between cells derived from subjects with or without asthma. Co-culture with mast cells did not affect the rate of proliferation or survival of ASM cells. Conclusion Our findings do not support a role for increased airway smooth proliferation and survival as the major mechanism driving ASM hyperplasia in asthma. Cite this as: D. Kaur, F. Hollins, R. Saunders, L. Woodman, A. Sutcliffe, G. Cruse, P. Bradding and C. Brightling, Clinical & Experimental Allergy, 2010 (40) 279, 288. [source] Cigarette smoke suppresses in vitro allergic activation of mouse mast cellsCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2009E. Mortaz Summary Background Mast cells are important effector cells in innate or acquired immunity that contribute to host defence. Excessive activation of mast cells can result in the development of allergic diseases, including atopic asthma. Mast cell activation by IgE and specific antigen induces the cells to release spasmogenic, vasoactive and pro-inflammatory mediators, which enhance airway smooth muscle contraction, vascular permeability and inflammatory cell recruitment. Recently, we have demonstrated that exposure of mast cells to cigarette smoke medium (CSM) triggered mast cells to produce chemokines. On the other hand, smoking may decrease the risk of allergic sensitization, which could be explained by a reduced IgE production or a diminished response of mast cells to activation of the IgE receptor. Objective In this study, we investigated the effect of CSM on the allergic activation of mast cells through IgE and antigen. Methods Primary cultured murine mast cells were exposed to CSM and activated with IgE and antigen or lipopolysaccharide (LPS). The release of granules, production of leukotrienes, chemokines and cytokines was determined in the supernatants by ELISA. The effect of CSM exposure on intracellular signalling, especially the nuclear factor (NF)-,B and extracellular signal-regulated kinase (Erk)1/2 pathways, was analysed by Western blotting. Results CSM suppressed IgE-mediated degranulation and cytokine release, but no effect was observed on leukotriene release. CSM induced phosphorylation of Erk1/2 in mast cells. In CSM-exposed mast cells, activating transcription factor (ATF)-1 was phosphorylated after stimulation with IgE/Ag. LPS-activated mast cells were not influenced by CSM. Conclusion Our study suggests that exposure to cigarette smoke may lead to a reduced allergic activation of mast cells without affecting their response to activation via e.g. bacterial-derived LPS. [source] Human mast cells express androgen receptors but treatment with testosterone exerts no influence on IgE-independent mast cell degranulation elicited by neuromuscular blocking agentsEXPERIMENTAL DERMATOLOGY, Issue 3 2010WenChieh Chen Please cite this paper as: Human mast cells express androgen receptors but treatment with testosterone exerts no influence on IgE-independent mast cell degranulation elicited by neuromuscular blocking agents. Experimental Dermatology 2010; 19: 302,304. Abstract:, Women predominate in the anaphylactic reactions to neuromuscular blocking agents (NMBA). The expression of oestrogen receptors has been demonstrated in mast cells and oestrogen treatment can enhance mast cell degranulation, but the influence of androgens remains largely unclear. Our immunocytochemical study showed the expression of androgen receptor (AR) in mast cells isolated from human foreskin as well as in two human mast cell lines, HMC-1 and LAD2. The amount of AR was most abundant in human skin mast cells as determined by real-time polymerase chain reaction analysis. Treatment of the HMC-1 mast cells with testosterone or 17,-oestradiol, alone or in combination with different NMBA, did not affect mast cell degranulation as measured by the release of ,-hexosaminidase. Our study shows for the first time the expression of AR in human skin mast cells. Further studies using primary human mast cell cultures are needed to understand whether and how sex hormones can influence mast cell activation. [source] The role of corticotropin-releasing hormone in immune-mediated cutaneous inflammatory diseaseEXPERIMENTAL DERMATOLOGY, Issue 3 2006Marina O' Kane Abstract:, Corticotropin-releasing hormone (CRH) coordinates the systemic stress response via hypothalamic-pituitary-adrenal (HPA) axis activation with subsequent modulation of the inflammatory response. Stress is known to affect expression of immune-mediated inflammatory diseases, many of which are associated with HPA axis abnormalities. HPA axis components including CRH and its receptors (CRH-R) exist in the skin and exhibit differential expression according to cell type, physiological fluctuations and disease states. This confirms a local functioning cutaneous HPA-like system. Peripheral CRH may exhibit proinflammatory effects. Animal studies confirm that peripheral CRH is required for induction of the inflammatory response in vivo. CRH and CRH-R are upregulated in inflammatory arthritis synovium and psoriatic skin. CRH may influence mast cell activation, direct modulation of immune cells, angiogenesis and induction of the novel orphan nuclear receptor NURR1. This transcription factor is part of the steroid/thyroid superfamily of related nuclear receptors that includes receptors for steroids, retinoids and vitamin D; ligands of these receptors are effective in treating psoriasis. The roles of CRH and NURR1 in psoriasis and inflammatory skin diseases, especially those associated with stress, remain to be elucidated. This stress may be psychological or physical. CRH, produced locally or delivered by peripheral nerves, may mediate interactions between a cutaneous HPA axis-like system and the central HPA axis , the ,brain-skin axis'. [source] Point mutations of 3BP2 identified in human-inherited disease cherubism result in the loss of functionGENES TO CELLS, Issue 11 2004S. M. Shahjahan Miah Adaptor protein 3BP2 positively regulates the high affinity IgE receptor (Fc,RI)-mediated activation of degranulation in mast cells. Genetic study identified the point mutations of 3BP2 gene in human-inherited disease cherubism. The multiple cysts in cherubism lesion of jaw bones are filled with the activated osteoclasts and stromal cells, including mast cells. By over-expression study using rat basophilic leukaemia RBL-2H3 mast cells, we have analysed the effect of the point mutations on the function of 3BP2 protein, which plays a positive regulatory role on Fc,RI-mediated mast cell activation. Over-expression of 3BP2 mutants suppressed the antigen-induced degranulation and cytokine gene transcription. Antigen-induced phosphorylation of Vav1, activation of Rac1, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen activated protein kinase (MAPK), inhibitor of nuclear factor ,B kinase (IKK) and nuclear factor of activated T cells (NFAT) were all impaired in the cells over-expressing the cherubism mutants of 3BP2. Furthermore, cherubism mutations of 3BP2 may abrogate the binding ability to interact with chaperone protein 14-3-3. These results demonstrate that over-expression of the mutant form of 3BP2 inhibits the antigen-induced mast cell activation. It suggests that point mutations of 3BP2 gene cause the dysfunction of 3BP2 in vivo. [source] The role of reactive oxygen species and nitric oxide in mast cell-dependent inflammatory processesIMMUNOLOGICAL REVIEWS, Issue 1 2007Emily J. Swindle Summary:, Reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS), including nitric oxide, are produced in cells by a variety of enzymatic and non-enzymatic mechanisms. At high levels, both types of oxidants are used to kill ingested organisms within phagocytes. At low levels, RNOS may diffuse outside cells where they impact the vasculature and nervous system. Recent evidence suggests that low levels of ROS produced within cells are involved in cell signaling. Along with these physiological roles, many pathological conditions exist where detrimental high-level ROS and RNOS are produced. Many situations in which ROS/RNOS are associated also involve mast cell activation. In innate immunity, such mast cells are involved in the immune response toward pathogens. In acquired immunity, activation of mast cells by cross-linking of receptor-bound immunoglobulin E causes the release of mediators involved in the allergic inflammatory response. In this review, we describe the principle pathways for ROS and RNOS generation by cells and discuss the existence of such pathways in mast cells. In addition, we examine the evidence for a functional role for ROS and RNOS in mast cell secretory responses and discuss evidence for a direct relationship between ROS, RNOS, and mast cells in mast cell-dependent inflammatory conditions. [source] Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell activationIMMUNOLOGY, Issue 4 2000S.-S. Chen Summary Reactive oxygen species (ROS) are known to modulate activities of a host of kinases, phosphatases and transcription factors. Rutin and chlorogenic acid (CGA) are the major polyphenolic antioxidants present in the small molecular fraction of smokeless tobacco leaf extracts, as ascertained by reverse-phase high-pressure liquid chromatography (HPLC) and mass spectrometry. Levels of intracellular ROS in resting versus antigen,immunoglobulin E (IgE)-challenged murine mast cells were measured at 510 nm by fluorescence-activated cell sorting (FACS) using carboxy-dichlorofluorescein (DCFH-DA). Enhanced ROS production was observed in IgE-sensitized mast cells following antigenic challenge. Rutin and CGA reduced ROS levels in antigen,IgE-activated mast cells. Concomitantly, they also profoundly inhibited histamine release by these activated mast cells. In contrast, rutin and CGA augmented the inducible cytokine messages, i.e. interleukin (IL)-10, IL-13, interferon-, (IFN-,), IL-6 and tumour necrosis factor-, (TNF-,) in IgE-sensitized mast cells following antigen challenge. This study indicates that tobacco polyphenolic antioxidants that quench intracellular ROS, differentially affect two effector functions of antigen,IgE-activated mast cells. This model system may be employed to determine the molecular target of polyphenols. The potential role of these polyphenolic antioxidants on IgE-mediated allergy in vivo depends on a balance of their differential effects on mast cell activation. [source] Gender difference, sex hormones, and immediate type hypersensitivity reactionsALLERGY, Issue 11 2008W. Chen Gender differences in the development and prevalence of human diseases have long been recognized. Immense interest grows in the understanding of the role of sex hormones in the homeostasis of immunity. Asthma predominates in boys before puberty and this gender preference reverses after puberty and in adulthood, when adult women tend to have a more severe disease, often recalcitrant to treatment. Atopic eczema in preschool children shows insignificant gender difference or male preponderance in different studies, with more adult females suffering from atopic eczema. The limited data on the prevalence of immediate hypersensitivity to hymenoptera venom show controversial results. Discrepancy exists regarding the gender difference in food allergy, with females reporting significantly more allergic reactions in questionnaire studies. In general, adverse reactions to nonionic iodinated radiocontrast media are more commonly observed in females. The course of allergic diseases varies unpredictably during pregnancy, whereas hormone replacement therapy in postmenopausal women usually has a favorable influence on the course of asthma. Experiments in rodents confirm an effect of estrogens on mast cell activation and allergic sensitization, while progesterone is shown to suppress histamine release but potentiate IgE induction. Dehydroepiandrosterone may antagonize the production of Th2 cytokines but the effect of testosterone and the other androgens remains less defined. Actual data from human studies are lacking. [source] Enhanced expression of mast cell growth factor and mast cell activation in the bladder following the resolution of trinitrobenzenesulfonic acid (TNBS) colitis in female rats,NEUROUROLOGY AND URODYNAMICS, Issue 6 2007Ruomei Liang Abstract Aims Chronic pelvic pain disorders often overlap. We have shown that acute colonic irritation can produce acute irritative micturition patterns and acutely sensitize bladder afferent responses to mechanical and chemical stimuli. We hypothesize that with time, colonic irritation can lead to neurogenic changes in the bladder and the development of chronic bladder sensitization. Methods Micturition patterns were measured in rats 60,90 days after the induction of trinitrobenzenesulfonic acid (TNBS) colitis in the resolution phase of this model. Total and activated mast cells (MCs) were quantified in the bladder, while mRNA levels of stem cell factor (SCF; a.k.a. MC growth factor) and nerve growth factor (NGF; a MC and nociceptive C-fiber stimulator) were quantified in the bladder and L6-S1 dorsal root ganglia (DRG). Results Following intra-rectal TNBS, voiding volume was reduced (P,<,0.005), while voiding frequency was increased (P,<,0.05), both by ,50%. Furthermore, both the percentage and density of activated bladder MCs were significantly elevated (P,<,0.05), although total MC counts were not statistically increased. At the molecular level, urinary bladder SCF expression increased twofold (P,<,0.005), as did NGF (P,<,0.01), while L6-S1 DRG levels were not significantly elevated. Conclusions Chronic cystitis in the rat as evidenced by changes in micturition patterns and the recruitment of activated MCs can occur during the resolution phase of TNBS colitis. These changes, of which MCs may play an important role, appear to be maintained over time and may occur via stimulation of convergent pelvic afferent input resulting in the upregulation of neurotrophic factors in the target organ. Neurourol. Urodynam. 26:887,893, 2007. © 2007 Wiley-Liss, Inc. [source] Immunoglobulin E antibodies enhance pulmonary inflammation induced by inhalation of a chemical haptenCLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2009C. B. Mathias Summary Background Occupational exposure to chemicals is an important cause of asthma. Recent studies indicate that IgE antibodies enhance sensitization to chemicals in the skin. Objective We investigated whether IgE might similarly promote the development of airway inflammation following inhalation of a contact sensitizer. Methods A model of chemical-induced asthma is described in which introduction of the low-molecular-weight compound, trinitrobenzene sulphonic acid (TNBS), via the respiratory tract was used for both sensitization and challenge. The role of IgE antibodies in the immune response to inhaled TNBS in this model was assessed by comparing the responses of wild-type (WT) and IgE-deficient (IgE,/,) mice on the BALB/c background. Reconstitution of circulating IgE levels by intravenous injection of IgE antibodies into IgE,/, mice before sensitization was performed to confirm the role of IgE in any differences observed between the responses of WT and IgE,/, mice. Results Intranasal challenge of TNBS-sensitized (but not sham-sensitized control mice) induced intense pulmonary inflammation. Macrophages, eosinophils and lymphocytes, including T, B, natural killer and natural killer T cells, were recruited to the airway and the animals displayed bronchial hyperresponsiveness (BHR) to methacholine. Serum levels of murine mast cell protease-1 (mMCP-1) were elevated suggesting mast cell activation. In contrast, the development of airway inflammation, recruitment of lymphocytes, induction of BHR and production of mMCP-1 were all significantly attenuated in IgE-deficient mice. Reconstitution of IgE,/, mice with IgE (of unrelated antigen specificity) before sensitization partially restored these features of asthma. Conclusion Our data indicate that IgE antibodies non-specifically enhance the development of airway inflammation induced by exposure to chemical antigens. [source] Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxisCLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009E. Ono Abstract Background Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. However, pathological evidence of the association between inflammatory mediators and human anaphylaxis is insufficient. Objective The aim of this study was to better understand the relationship between in vivo production of inflammatory mediators and the pathogenesis of anaphylaxis. We also sought to evaluate mast cell activation in anaphylaxis. Methods We measured the concentrations of various inflammatory mediators in urine samples, which were collected from 32 anaphylactic patients during the onset of anaphlaxis and during clinical remission, 21 patients with asthma on acute exacerbation and 15 healthy control subjects. Blood and urine specimens were collected from the patients after provocation test. Urinary leukotriene E4 (LTE4), 9,, 11,-prostaglandin F2 (9,, 11,-PGF2), eosinophil-derived neurotoxin (EDN) and leukotriene B4 glucuronide (LTBG) concentrations were determined by enzyme immunoassay, and the activity of plasma platelet-activating factor acetylhydrolase and serum tryptase concentration were measured using commercially available kits. Results Significantly higher concentrations of urinary LTE4 and 9,, 11,-PGF2, which immediately decreased during clinical remission, were observed in the anaphylactic patients than in asthmatic patients on acute exacerbation and healthy control subjects. Concentrations of EDN and LTBG were not significantly different among the anaphylactic patients, asthmatic patients on acute exacerbation and healthy subjects. There was a significant correlation between urinary LTE4 and 9,, 11,-PGF2 concentrations in the anaphylactic patients (r=0.672, P=0.005, n=32). In addition, LTE4 concentration in patients with anaphylactic shock is significantly elevated compared with that in patients without anaphylactic shock. Conclusions This is a report on the significant increase in urinary LTE4 and 9,, 11,-PGF2 concentrations during anaphylaxis. Urinary LTE4 and 9,, 11,-PGF2 concentrations may be a reliable marker of endogenous production of inflammatory mediators associated with anaphylaxis. [source] Leukotrienes and other mast cell mediators cause asthmatic airway obstructionCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2004S.-E. Dahlén Summary From an evolutionary perspective, bronchoconstriction is a highly conserved mechanism for defence against stimuli that are noxious for the lung and airways. The presence of mast cells in all layers of the airways makes them ideally situated to function as sensors of environmental changes that require such a host defence reaction. In addition to being activated by high affinity IgE receptors, many other trigger factors are known to activate signal transduction pathways leading to mast cell degranulation. This includes changes in the physical and chemical composition of the environment, exposure to endotoxin and other microbial factors acting on Toll-like receptors [1], intake of certain drugs and in particular virtually all nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects with the peculiar syndrome aspirin-intolerant asthma (AIA) [2]. Irrespective of the trigger, the consequence of mast cell activation is release of biologically active smooth muscle stimulating mediators as well as the secretion of cytokines, chemotactic factors and enzymes that are believed to trigger further cascades contributing to long-term tissue remodelling and chronic airway inflammation. [source] A crucial role for macrophages in the pathology of K/B,×,N serum-induced arthritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2005Samuel Solomon Abstract Autoantibodies in the form of immune complexes are known to be crucial mediators in initiating inflammation in a variety of autoimmune diseases. This has been well documented in the anti-collagen,II antibody-induced arthritis animal model for a long time now. Recently, in the K/B,×,N mouse model (the F1 of the TCR-transgenic KRN and the diabetic NOD mice), anti-glucose-6-phosphate isomerase (GPI) autoantibodies have been shown to induce arthritis. Experimental work in the K/B,×,N model demonstrated key roles of autoantigenic immune complexes activating the alternative pathway of complement, the subsequent association with C5aR and Fc,RIII-mediated cell activation and production of the inflammatory cytokines IL-1 and TNF-,, finally leading to joint destruction. The presence of high amounts of inflammatory cytokines and matrix-degrading proteases at sites of inflammation obviously put the cytokine-producing macrophages as the next target for investigation in this model. Here, we show that mice depleted of macrophages by clodronate liposome treatment are completely resistant to K/B,×,N serum-induced arthritis. Reconstituting clodronate liposome-treated mice with macrophages from naive animals could reverse this resistance. Also, we found that deficiencies in the Wiskott-Aldrich syndrome protein and CD40, which are both implicated in macrophage activation, chemotaxis and phagocytosis, are not essential in serum-induced arthritis. Mast cell degranulation was seen in arthritogenic serum-treated mice even in the absence of macrophages, possibly suggesting that mast cell degranulation/activation acts hierarchically before macrophages in the inflammatory cascade of anti-GPI antibody-induced arthritis. [source] | |||||||||||||||||||||||||