TY - JOUR. T1 - Involvement of p38 MAP kinase and Smad3 in TGF-β-mediated mast cell functions. AU - Funaba, Masayuki. AU - Ikeda, Teruo. AU - Murakami, Masaru. AU - Ogawa, Kenji. AU - Nishino, Yoshii. AU - Tsuchida, Kunihiro. AU - Sugino, Hiromu. AU - Abe, Matanobu. PY - 2006/12/1. Y1 - 2006/12/1. N2 - Transforming growth factor-β (TGF-β) modulates functions of bone marrow-derived cultured mast cells (BMMCs); cell maturation (up-regulation of mouse mast cell proteases (mmcps)), growth arrest and migration. We investigated the roles of p38 MAP kinase and Smad3 in TGF-β-mediated cell responses in BMMCs. Treating BMMCs with TGF-β induced the phosphorylation of p38 within 2 h and persisted for 24 h. The involvement of p38 in TGF-β-induced cell responses depended upon mast cell functions; it was necessary for up-regulation of mmcp-1 and migration, but not for up-regulation of mmcp-7 and inhibition of metabolic activity. New protein synthesis was required for the up-regulation of mmcp-1 but not ...

Mast cells may activate fibroblasts and contribute to remodeling processes in the lung. However, the mechanism behind these actions needs to be further investigated. Fibroblasts are major regulators of on-going remodeling processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be activated by serine proteases, such as the mast cell mediator tryptase. The objective in this study was to investigate the effects of mast cells and specifically mast cell tryptase on fibroblast migration and the role of PAR2 activation. Human lung fibroblasts (HFL-1) were cultured together with human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with either conditioned medium from LAD2 cells or tryptase. Analyses of immunological stimulation of mast cells by IgE/anti IgE in the co-culture system were also performed. The importance of PAR2 activation by mast cells and mast cell tryptase for the migratory effects of fibroblasts was investigated by pre-treatment with the PAR2

TY - JOUR. T1 - Proliferative quiescence of normal mast cells resembles that of cold-sensitive mutant mastocytoma cells. Dominant expression of the quiescent state in heterokaryons. AU - Laeng, H.. AU - Harris, David T.. AU - Schindler, R.. PY - 1985. Y1 - 1985. N2 - Normal murine peritoneal mast cells were fused to serum-deprived, non-proliferating cells of a cultured subline (41-SB-4) of the P-815 murine mastocytoma. Upon reincubation in medium containing 10% horse serum for 48 h, mono- and binuclear 41-SB-4 cells reentered S phase of the cell cycle, while mast cell × 41-SB-4 heterokaryons as well as mono- and binuclear mast cells remained in proliferative quiescence, indicating dominant expression of the quiescent state of mast cells. The quiescent state of normal mast cells thus resembles that of cold-sensitive (cs) mutant cells (21-F) of the undifferentiated P-815 mastocytoma: at the non-permissive temperature of 33 °C, the 21-F cells were found to enter a state of quiescence which is ...

Background: Mast cells infiltrate the bronchial smooth muscle (BSM) in asthmatic patients, but the mechanism of mast cell adhesion is still unknown. The adhesion molecules CD44 (i.e. hyaluronate receptor) and CD51 (i.e. vitronectin receptor) are widely expressed and bind to many extracellular matrix (ECM) proteins. The aims of the study are (i) to identify the role of ECM in mast cell adhesion to BSM and (ii) to examine the role of CD51 and CD44 in this adhesion.. Methods: Human lung mast cells, human mast cell line (HMC-1), and BSM cells from control donors or asthmatic patients were cultured in the presence/absence of various cytokines. Mast cell-BSM interaction was assessed using 3H-thymidine-pulsed mast cells, confocal immunofluorescence, or electron microscopy. Adhesion molecules expression and collagen production on both cell types were evaluated by quantitative RT-PCR, western blot, and flow cytometry.. Results: Mast cell adhesion to BSM cells mostly involved type I collagen of the ECM. ...

BACKGROUND: In asthma and other allergic disorders, the activation of mast cells by IgE and antigen induces the cells to release histamine and other mediators of inflammation, as well as to produce certain cytokines and chemokines. To search for new mast cell products, we used complementary DNA microarrays to analyze gene expression in human umbilical cord blood-derived mast cells stimulated via the high-affinity IgE receptor (Fc(epsilon)RI).. RESULTS: One to two hours after Fc(epsilon)RI-dependent stimulation, more than 2,400 genes (about half of which are of unknown function) exhibited 2-200 fold changes in expression. The transcriptional program included changes in the expression of IL-11 and at least 30 other cytokines and chemokines. Human mast cells secreted 130-529 pg of IL-11/106 cells by 6 h after stimulation with anti-IgE.. CONCLUSION: Our initial analysis of the transcriptional program induced in in vitro-derived human mast cells stimulated via the Fc(epsilon)RI has identified many ...

Mast cell activation causes degranulation and release of cytokines, thereby promoting inflammation. The aim of this study was to investigate the inhibitory effect of CDK4/6 inhibition on mast cell activation in vitro and in vivo. RBL-2H3 rat basophilic leukemia cells (BLCs) and mouse bone marrow-derived mast cells (BMMCs) were sensitized with anti-dinitrophenol (DNP) immunoglobulin (Ig)E antibodies, stimulated with DNP-human serum albumin (HSA) antigens, and treated with the CDK4/6 inhibitor palbociclib. Histological stains were applied to reveal cytomorphological changes. Murine IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin (OVA)-induced active systemic anaphylaxis (ASA) models were used to examine palbociclib effects on allergic reactions in vivo. Western blots were performed to detect the expression of cell signaling molecules associated with mast cell activation. Activated BLCs and BMMCs released copious granule-related mediators (histamine and β-hexosaminidase), which was reduced

TY - JOUR. T1 - Mast cell deficiency results in the accumulation of preadipocytes in adipose tissue in both obese and non-obese mice. AU - Ishijima, Yasushi. AU - Ohmori, Shinya. AU - Ohneda, Kinuko. PY - 2014. Y1 - 2014. N2 - Mast cells have been suggested to play key roles in adipogenesis. We herein show that the expression of preadipocyte, but not adipocyte, marker genes increases in the white adipose tissue of mast cell-deficient (KitW-sh/W-sh) mice under both obese and non-obese conditions. In vitro culturing with adipogenic factors revealed increased adipocytes differentiated from the KitW-sh/W-sh stromal vascular fraction, suggesting the accumulation of preadipocytes. Moreover, the increased expression of preadipocyte genes was restored by mast cell reconstitution in the KitW-sh/W-sh mice. These results suggest positive effects of mast cells on the preadipocyte to adipocyte transition under both physiological and pathological conditions.. AB - Mast cells have been suggested to play key ...

Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it is not observed when SCF is administered to mice containing dermal mast cells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms of SCF, and ...

Intravital multiphoton microscopy has provided insightful information of the dynamic process of immune cells in vivo. However, the use of exogenous labeling agents limits its applications. There is no method to perform functional imaging of mast cells, a population of innate tissue-resident immune cells. Mast cells are widely recognized as the effector cells in allergy. Recently their roles as immunoregulatory cells in certain innate and adaptive immune responses are being actively investigated. Here we report in vivo mouse skin mast cells imaging with two-photon microscopy using endogenous tryptophan as the fluorophore. We studied the following processes. 1) Mast cells degranulation, the first step in the mast cell activation process in which the granules are released into peripheral tissue to trigger downstream reactions. 2) Mast cell reconstitution, a procedure commonly used to study mast cells functioning by comparing the data from wild type mice, mast cell-deficient mice, and mast-cell deficient

c-kit ligand (KL) activated mouse bone marrow-derived mast cells (BMMC) for the dose- and time-dependent release of arachidonic acid from cell membrane phospholipids, with generation of leukotriene (LT) C4 in preference to prostaglandin (PG)D2. KL at concentrations of 10 ng/ml elicited half-maximal eicosanoid generation and at concentrations of , 50 ng/ml elicited a maximal generation of approximately 15 ng LTC4 and 1 ng PGD2 per 10(6) cells, with 20% net beta-hexosaminidase release 10 min after stimulation. Of the other cytokines tested, none, either alone or in combination with KL, elicited or modulated the immediate phase of mediator release by BMMC, indicating strict specificity for KL. Activation of BMMC in response to KL was accompanied by transient phosphorylation of cytosolic phospholipase A2 and reversible translocation of 5-lipoxygenase to a cell membrane fraction 2-5 min after stimulation, when the rate of arachidonic acid release and LTC4 production were maximal. BMMC continuously ...

Resveratrol, a polyphenol abundant in peanuts, red wine and the skin of grapes, has been shown to have anti-cancer, anti-oxidant and anti-inflammatory activities, and may also have beneficial effects on allergic inflammation. We investigated the effects of resveratrol on human mast cell activation in comparison to the anti-allergy drug tranilast. In LAD2 mast cells, both resveratrol and tranilast inhibited degranulation induced by the mast cell activators substance P, IgE/anti-IgE, and compound 48/80. Resveratrol inhibition was immediate, preventing degranulation when added simultaneously to physiological stimuli, and the effect was sustained for up to 24 hrs. The inhibitory effect was not cAMP dependent, but may be attributable to calcium modulation, as resveratrol, and to a lesser extent tranilast, prevented substance P-induced increases in intracellular calcium. Resveratrol attenuated substance P-induced TNF and MCP-1 production and inhibited IgE-mediated release of cysteinyl leukotrienes, whereas

TY - JOUR. T1 - Leflunomide inhibits PDK1/Akt pathway and induces apoptosis of human mast cells. AU - Sawamukai, Norifumi. AU - Saito, Kazuyoshi. AU - Yamaoka, Kunihiro. AU - Nakayamada, Shingo. AU - Ra, Chisei. AU - Tanaka, Yoshiya. PY - 2007/11/15. Y1 - 2007/11/15. N2 - Mast cells release many inflammatory mediators that play an important role not only in allergic diseases but also in chronic inflammatory diseases, autoimmune diseases, and others. A lot of mast cells exist in synovium of rheumatoid arthritis, and it is known that synovitis does not occur in mast cell-deficient mice. Thus, it is thought that mast cells play a very important role in rheumatoid arthritis pathogenesis. Leflunomide is a drug used clinically in the treatment of rheumatoid arthritis. We used clinical doses of 2-cyano-3-hydroxy-N-(4-trifluoromethylphenyl)-butenamide (A77 1726), which is an active metabolite of leflunomide, and decreased the number of viable human primary mast cells in a concentration-dependent manner. ...

Exposure to monomeric IgE in vitro markedly upregulated the ability of mature mouse peritoneal mast cells or mouse BMCMCs or cloned mast cells to bind IgE. Two separate lines of evidence indicate that this response largely, if not entirely, reflected the increased surface expression of FcεRI. First, while mouse mast cells also express FcγRII/ III ((17), (18)), which can bind IgE immune complexes ((18)), virtually all of the binding of monomeric IgE to mouse mast cells that is detectable under the conditions used in our experiments reflects binding of the ligand to a single class of high affinity binding sites, i.e., FcεRI ((18)). Second, we used anti-IgE to immunoprecipitate surface-bound IgE, and associated IgE receptors, from lysates of BMCMCs that had been first incubated with or without IgE at 5 μg/ml for 21 h and then exposed briefly to excess IgE just before recovery for flow cytometry and Western blot analysis. We found that, in comparison to aliquots of the same mast cell population ...

TY - JOUR. T1 - Progress in allergy signal research on mast cells. T2 - Signal regulation of multiple mast cell responses through FcεRI. AU - Yamasaki, Shou. AU - Saito, Takashi. PY - 2008/4/8. Y1 - 2008/4/8. N2 - The crosslinking of FcεRI by IgE and antigen (Ag) on mast cells initiates activation cascades that lead to allergic responses. Although it was thought that IgE binding to FcεRI is a passive sensitization, recent reports suggest that IgE actively promotes mast cell survival in the absence of Ag. However, it is largely unknown how these distinct responses are delivered through the same receptor, FcεRI, depending on the types of stimli. As an underlying molecular mechanism for the generation of diverse responses through FcεRI, we found that the quantity and the duration of the signal through the FcεRI γ chain (FcRγ) determine different mast cell responses. Furthermore, FcRγ-mediated sustained Erk activation is critical for IgE-induced mast cell survival through autocrine ...

In this study the diversity of mast cell proteases and some of the factors regulating mast cell growth and protease expression were examined in rodents. Five proteases were isolated from mouse small intestinal mucosa and their substrate specificities defined. The isolated proteases were all of mast cell origin and were chymotrypsin-like in their substrate specificities. The proteases were all identified as variants of mouse mast cell protease-1 which differed only in their carbohydrate moieties. Despite the fact that these enzymes shared a common core polypeptide they all differed significantly in the rate at which they hydrolysed synthetic substrates and in the rates at which they were inhibited by α1-proteinase inhibitor. A related, but distinct protease was isolated from peritoneal cavity mast cells of mice. This enzyme, also a chymase, had N-terminal sequence identity with mouse mast cell protease-4. This enzyme was not inhibited by α1-proteinase inhibitor. Factors which regulate mast cell ...

Mast cells are best known for their function in hypersensitive reactions, where aggregation of FcRI leads to the release of mast cell mediators leading to hypersensitive symptoms. although activation-induced success is certainly suffered, suggesting a minimal function for Bcl-XL, Bcl-2, Mcl-1 and Bcl-w. Reducing but not really amounts by siRNA inhibited activation-induced mast cell success. We also demonstrate that mast cell phrase of Bfl-1 is certainly raised in birch-pollen-provocated epidermis and in lesions of atopic dermatitis and psoriasis sufferers. Used jointly, our outcomes high light Bfl-1 as a main effector in activation-induced individual mast cell success. Launch Mast cells are known to end up being central regulators and effectors in allergic illnesses. When a multivalent antigen binds to IgE occupying the high affinity receptor for IgE (FcRI), receptor aggregation and following mast cell account activation takes place. This total result in mast cell degranulation, adjustments in ...

The mechanism of chronic mast cell activation in asthma is unclear. Monomeric immunoglobulin (Ig)E in the absence of allergen induces mediator release from rodent mast cells, indicating a possible role for IgE in the continued activation of mast cells within the asthmatic bronchial mucosa. In this study it was investigated whether monomeric IgE induces Ca2+ influx and mediator release from human lung mast cells (HLMC). Purified HLMC were cultured for 4 weeks and then exposed to monomeric human myeloma IgE. Ratiometric Ca2+ imaging was performed on single fura-2-loaded cells. Histamine release was measured by radioenzymatic assay; leukotriene C4 (LTC4) and interleukin (IL)-8 were measured by ELISA. At concentrations experienced in vivo, monomeric IgE induced dose-dependent histamine release, LTC4 production and IL-8 synthesis. This was associated with a rise in cytosolic free Ca2+. Enhanced histamine release was still evident 1 week after initial exposure to IgE suggesting that continued exposure ...

Previous in vitro studies have shown biphasic effects of adenosine on mast cell activity; however, the receptor subtypes that mediate the inhibitory effects of adenosine are still controversial (Peachell et al., 1991; Yip et al., 2009). Mast cells express two distinct Gs-coupled adenosine receptors; their biologic roles have not been comprehensively defined, especially in vivo. Since activation of Gs-coupled adenosine receptors increases intracellular cAMP, we hypothesized that the inhibitory effects of adenosine on mast cells are mediated by the Gs-coupled adenosine receptors. In this study, we used both genetically modified animal models and mast cell cultures to comprehensively investigate the role of Gs-coupled adenosine receptors on mast cells both in vitro and in vivo. First, our data demonstrate a potent inhibitory effect of the nonhydrolyzable adenosine analog NECA on IgE-induced mast cell degranulation; this inhibitory effect of NECA was abolished by the genetic deletion of the A2B but ...

TY - JOUR. T1 - Time- and concentration-dependent effects of exogenous serotonin and inflammatory cytokines on mast cell function. AU - Gruba, Sarah M.. AU - Meyer, Audrey F.. AU - Manning, Benjamin M.. AU - Wang, Yiwen. AU - Thompson, John W.. AU - Dalluge, Joseph J.. AU - Haynes, Christy L.. PY - 2014/2/21. Y1 - 2014/2/21. N2 - Mast cells play a significant role in both the innate and adaptive immune response; however, the tissue-bound nature of mast cells presents an experimental roadblock to performing physiologically relevant mast cell experiments. In this work, a heterogeneous cell culture containing primary culture murine peritoneal mast cells (MPMCs) was studied to characterize the time-dependence of mast cell response to allergen stimulation and the time- and concentration-dependence of the ability of the heterogeneous MPMC culture to uptake and degranulate exogenous serotonin using high performance liquid chromatography (HPLC) coupled to an electrochemical detector. Additionally, ...

To our knowledge, this study is the first to report a regulatory function of tetraspanin CD151 in mast cells. Moreover, it is one of the first reports, to our knowledge, addressing the signaling mechanism of modulation of mast cell activation by any member of the tetraspanin family. In the present study, we demonstrated that CD151 deficiency exacerbated late-phase allergic inflammation in mice in vivo and enhanced proinflammatory cytokine production by cultured BMMCs ex vivo. Moreover, BMMCs deficient in CD151 showed enhanced and sustained FcεRI-induced ERK1/2 and Akt phosphorylation compared with WT cells. Conversely, CD151 deficiency had no effect on mast cell degranulation or the acute phase of PCA. Thus, our data demonstrate that the tetraspanin CD151 functions to selectively inhibit late-phase anaphylaxis responses and the de novo synthesis of cytokines by activated mast cells.. Mast cells possess mechanisms for fine tuning cellular activation that allow initial FcεRI-mediated signaling ...

Latexin, a protein possessing inhibitory activity against rat carboxypeptidase A1 (CPA1) and CPA2, is expressed in a neuronal subset in the cerebral cortex and cells in other neural and non-neural tissues of rat. Although latexin also inhibits mast-cell CPA (MCCPA), the expression of latexin in rat mast cells has not previously been confirmed. In the present study we examined the expression and subcellular localization of latexin in rat peritoneal mast cells. Western blot and reverse-transcriptase-mediated PCR analyses showed that latexin was contained and expressed in the rat peritoneal mast cells. Immunocytochemically, latexin immunofluorescence was localized on granular structures distinct from MCCPA-, histamine- or cathepsin D-immunopositive granules. Immunoelectron microscopy revealed that latexin was associated with a minority population of granules. The latexin-associated granules were separated from MCCPA- or histamine-containing granules on a self-generating density gradient of ...

Background and objective:Gingival bleeding reduction in smokers has been associated with decreased blood vessel density. The mechanism of suppressive effect of cigarette smoking on blood vessel density is not precisely defined. The aim of this study was to evaluate the impact of smoking on angiogenesis by assessing mast cells density and VEGF expression in chronic periodontitis. Materials& Methods: 52 paraffin embedded block of gingiva tissues with periodontitis obtained from 30 nonsmokers and 22 smokers undergoing flap surgery were examined immunohistochemically for VEGF expression. Mast cell counts was completed on toluidine blue stained slides. Exposure to cigarette smoking was calculated by the number of packs × year. Patients were classified into 4 groups based on the number of smoked cigarettes. The correlation between VEGF expression and mast cell counts was evaluated and compared in nonsmokers and smokers. Results: The mean number of mast cells (p=0.004) and average value of VEGF expression (p

Author(s): Hata, D; Kawakami, Y; Inagaki, N; Lantz, CS; Kitamura, T; Khan, WN; Maeda-Yamamoto, M; Miura, T; Han, W; Hartman, SE; Yao, L; Nagai, H; Goldfeld, AE; Alt, FW; Galli, SJ; Witte, ON; Kawakami, T | Abstract: We investigated the role of Brutons tyrosine kinase (Btk) in FcepsilonRI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these mice exhibited significant abnormalities in FcepsilonRI-dependent function. xid mice primed with anti-dinitrophenyl monoclonal IgE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast cells derived from the bone marrow cells of xid or btk null mice exhibited mild impairments in degranulation, and more profound defects in the production of several cytokines, upon FcepsilonRI

phdthesis{d683936c-1726-4ede-86a7-193f0162cd84, abstract = {Mast cell are found throughout the body, but are especially prominent in tissues that have direct contact with the external milieu such as the skin, gastrointestinal tract and lungs. Mast cells are commonly recognized for their detrimental role in allergic reactions and can, upon activation through the high-affinity receptor for IgE (FcεRI), rapidly produce and secrete many of the mediators responsible for the typical symptoms in urticaria, asthma and rhinitis. However, increasing amount of data show that mast cells have important, even vital, roles in host defence against bacteria, viruses, parasites and venoms. Mast cells exist as two different subtypes, MCT (mucosal mast cells) and MCTC (connective tissue mast cells). These two subtypes differ in their molecular expression and distribution in the body. MCT are for example the dominating subtype in the lungs, while MCTC are most common in the skin and the gastrointestinal tract. ...

TY - JOUR. T1 - Diamine oxidase-gold ultrastructural localization of histamine in isolated human lung mast cells stimulated to undergo anaphylactic degranulation and recovery in vitro. AU - Dvorak, Ann M.. AU - Morgan, Ellen S.. AU - Schleimer, Robert P.. AU - Lichtenstein, Lawrence M.. PY - 1996/1/1. Y1 - 1996/1/1. N2 - A new enzyme-affinity-gold ultrastructural method makes use of the affinity of the enzyme, diamine oxidase coupled to gold, for its substrate, histamine, for localization of histamine in isolated human lung mast cells (HLMCs). The method works with routinely prepared ultrastructural samples, thereby allowing precise identification of ultrastructural structures that contain histamine. We used this method to identify the release of histamine from granule stores in anti-immunoglobulin-E (IgE)-stimulated HLMCs and the replacement of histamine in secretory granules of HLMCs during recovery from anaphylactic degranulation in vitro. The findings show that electron-dense granules in ...

Mast cells (MC) have been mainly studied as key effectors in allergic diseases and inflammatory conditions such hypersensitivity reactions, asthma, atopic dermatitis and multiple sclerosis. Following the crosslinkage of membraneous FcεRI, by antigens, a large number of chemical mediators are secreted. This event leads to the recruitment and activation of basophils and eosinophils that sustain the inflammatory response. The role of mast cells, however, is not limited to the initiation of allergic response but they are also fundamental players in the innate immune response; for example they can be activated directly by pathogens through a family of pattern recognition receptors called Toll-like receptors (TLRs). In particular, TLR2 and 4 seem to be crucial to the mast cell response to pathogens. In rodents, mast cells respond to lipopolysaccharide through their TLR4s by the release of pro-inflammatory cytokines without concurrent degranulation or they can degranulate following peptidoglycan ...

TY - JOUR. T1 - Pediatric Expression of Mast Cell Activation Disorders. AU - Broesby-Olsen, Sigurd. AU - Carter, Melody. AU - Kjaer, Henrik Fomsgaard. AU - Mortz, Charlotte Gotthard. AU - Møller, Michael Boe. AU - Kristensen, Thomas Kielsgaard. AU - Bindslev-Jensen, Carsten. AU - Agertoft, Lone. PY - 2018/8. Y1 - 2018/8. N2 - Mast cell activation disorders is a term proposed to cover diseases and conditions related to activation of mast cells and effects of mast cell mediators. In its broadest sense, the term encompasses a wide range of diseases from allergic asthma to rhinoconjunctivitis, urticaria, food allergy, anaphylaxis, mastocytosis, and other conditions where MC activation is contributing to the pathogenesis. This article focuses on clinical presentations, challenges, and controversies in pediatric mastocytosis and gives an overview of current knowledge and areas in need of further research.. AB - Mast cell activation disorders is a term proposed to cover diseases and conditions related ...

Expression of Mast Cell Proteases Correlates with Mast Cell Maturation and Angiogenesis during Tumor Progression. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.

Mast cells donate to allergy through IgE-dependent activation the high-affinity IgE receptor FcεRI. receptor gain-of-function human mast cell line HMC-1. Unlike MS4A2 MS4A2trunc did not traffic to the cytoplasmic membrane but instead was associated with the nuclear membrane. Overexpression of MS4A2trunc induced human lung mast cell death and profoundly inhibited HMC-1 cell proliferation by inducing G2-phase cell cycle arrest and apoptosis. Thus we have identified a novel splice variant of MS4A2 that might be important in the regulation of human mast cell proliferation and survival. This finding demonstrates that the MS4A2 gene has multiple roles extending beyond the rules of acute sensitive reactions. By understanding the systems regulating its function it could be feasible to induce its manifestation in mast cells cells had been then transformed using the MS4A2 clones and plated from agar plates including 100 μg/ml ampicillin with 100 μl of IPTG and 20 μl of X-galactose added. Transformed ...

Its official: though weve long suspected it, we can now add eczema/atopic dermatitis to the list of histamine/mast cell related conditions.. A new study [1] recently proved, for the first time in humans, that mast cells (the pesky little buggers that house histamine in the body) are a key culprit in causing eczema (also known as atopic dermatitis). The researchers also revealed that a protein known as STAT5, plays an important role in the equation by triggering major mast cell increases in some.. They now think the key to prevent or better treat eczema lies in blocking STAT5, which along with histamine, lives in our mast cells.. Lost?. Ok, so, mast cells are kind of the army barracks where histamine and others live. When our bodys in trouble, mast cells open their doors, allowing histamine and other inflammatory elements to be released in order to get to the site of an injury or infection, to get the healing process started. In addition to histamine, a number of other inflammatory molecules ...

Mast cells are present in limited numbers in normal human synovium, but in rheumatoid arthritis and other inflammatory joint diseases this population can expand to constitute 5% or more of all synovial cells. Recent investigations in a murine model have demonstrated that mast cells can have a critical role in the generation of inflammation within the joint. This finding highlights the results of more than 20 years of research indicating that mast cells are frequent participants in non-allergic immune responses as well as in allergy. Equipped with a diversity of surface receptors and effector capabilities, mast cells are sentinels of the immune system, detecting and delivering a first response to invading bacteria and other insults. Accumulating within inflamed tissues, mast cells produce cytokines and other mediators that may contribute vitally to ongoing inflammation. Here we review some of the non-allergic functions of mast cells and focus on the potential role of these cells in murine and human

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease, which is characterized by inflammation of synovial joints leading to the destruction of cartilage and bone. Infiltrating mast cells can be found within the inflamed synovial tissue, however their role in disease pathogenesis is unclear. Therefore we have studied the role of mast cells during different phases of experimental arthritis. We induced collagen-induced arthritis (CIA), the most frequently used animal model of arthritis, in an inducible mast cell knock-out mouse and determined the effect of mast cell depletion on the development and severity of arthritis. Depletion of mast cells in established arthritis did not affect clinical outcome. However, depletion of mast cells during the preclinical phase resulted in a significant reduction in arthritis. This reduction coincided with a decrease in circulating CD4+ T cells and inflammatory monocytes but not in the collagen-specific antibody levels. Mast cell depletion resulted in reduced

In addition to their central role in allergy, mast cells are involved in a wide variety of cellular interactions during homeostasis and disease. In this review, we discuss the ability of mast cells to extend their mechanisms for intercellular communication beyond the release of soluble mediators. These include formation of mast cell synapses on antigen presenting surfaces, as well as cell-cell contacts with dendritic cells and T cells. Release of membrane bound exosomes also provide for the transfer of antigen, mast cell proteins, and RNA to other leukocytes. With the recognition of the extended role mast cells have during immune modulation, further investigation of the processes in which mast cells are involved is necessary. This reopens mast cell research to exciting possibilities, demonstrating it to be an immunological frontier ...

TY - JOUR. T1 - BLT2 is upregulated in allergen-stimulated mast cells and mediates the synthesis of Th2 cytokines. AU - Cho, Kyung Jin. AU - Seo, Ji Min. AU - Lee, Min-Goo. AU - Kim, Jae-Hong. PY - 2010/11/15. Y1 - 2010/11/15. N2 - Mast cells are effector cells that mediate the allergic response through Ag stimulation of IgE bound to FcεRI. In allergic reactions, cross-linking of the surface receptors for IgE on mast cells results in the synthesis of Th2 cytokines such as IL-4 and IL-13, which are critical for the initiation and progression of the allergic response. Despite the important roles of these cytokines, the signaling mechanism by which Ag stimulation mediates the production of IL-4 and IL-13 in mast cells is not clearly understood. In the present study, we found that Ag-stimulated bone marrow-derived mast cells (BMMCs) highly upregulated the expression of BLT2, a leukotriene B 4 receptor, and that blockade of BLT2 with the specific antagonist LY255283 or small interfering RNA ...

Mast cells are connected with swelling and fibrosis. led to renin-dependent protracted circulation recovery. This demonstrates that mast cell renin is PIK-294 supplier definitely energetic in situ and the following ANG II can modulate intrarenal vascular level of resistance in the UUO kidney. Jointly, the data Rabbit Polyclonal to STEA3 demonstrate that mast cells are essential to the advancement of renal fibrosis in the 14-day time UUO kidney. Since renin is definitely present in human being kidney mast cells, our function recognizes potential focuses on in the treatment of renal fibrosis. is definitely the quantity of photo slides for a provided pet. Renin activity (ANG I radioimmunoassay). Renin activity was assessed in separated mast cell lysate (rat kidney and human being kidney), as previously reported (32, 48, 54). The recognition limit was 0.01 pmol (32). Remote mast cells had been lysed in 1 ml of PBS by four cycles of freeze-thaw. The renin-containing lysates had been after that ...

Mast cell (MC) differentiation, survival, and activation are controlled by the membrane tyrosine kinase c-Kit upon interaction with stem cell factor (SCF). Here we describe a single point mutation induced by N-ethyl-N-nitrosurea (ENU) mutagenesis in C57BL/6J mice-an A to T transversion at position 2388 (exon 17) of the c-Kit gene, resulting in the isoleucine 787 substitution by phenylalanine (787F), and analyze the consequences of this mutation for ligand binding, signaling, and MC development. The Kit(787F/787F) mice carrying the single amino acid exchange of c-Kit lacks both mucosal and connective tissue-type MCs. In bone marrow-derived mast cells (BMMCs), the 787F mutation does not affect SCF binding and c-Kit receptor shedding, but strongly impairs SCF-induced cytokine production, degranulation enhancement, and apoptosis rescue. Interestingly, c-Kit downstream signaling in 787F BMMCs is normally initiated (Erk1/2 and p38 activation as well as c-Kit autophosphorylation) but fails to be ...

Mast cells are tissue-resident hematopoietic cells. Because infectious agents enter the host through environmentally exposed barriers, such as the skin, gastrointestinal tract, and respiratory tract, mast cells are poised to be one of the first cell types to respond to invading pathogens. Furthermore, mast cells express a wide array of pattern recognition receptors that endow them with the ability to respond to a broad range of stimuli, such as infections and pathogenic conditions (51). It is well established that mast cells play crucial immune surveillance roles during bacterial and parasitic infections (8, 12). In contrast, the role of mast cells in the immune surveillance of viral infections has received less attention. In the current study, we examined the role of mast cells in sensing IAV infection and initiating the subsequent inflammatory response.. A primary rationale for our work stems from the recent work by Teijaro et al. (6), who demonstrated that blunting the cytokine storm ...

TY - JOUR. T1 - Novel Site-Specific Mast Cell Subpopulations in the Human Lung.. AU - Andersson, Cecilia K. AU - Mori, Michiko. AU - Bjermer, Leif. AU - Löfdahl, Claes-Göran. AU - Erjefält, Jonas. PY - 2009. Y1 - 2009. N2 - BACKGROUND: Lung mast cells are stereotypically divided into connective tissue (MCTC) and mucosal (MCT) mast cells. This study tests the hypothesis that each of these subtypes can be divided further into site-specific populations created by the microenvironment within each anatomic lung compartment. METHODS: To study mast cells under non-inflamed conditions surgical resections and bronchial and transbronchial biopsies from non-smoking individuals were obtained to investigate morphometric and molecular characteristics of mast cell populations in multiple lung structures by immunohistochemistry and electron microscopy. RESULTS: MCT and MCTC coexisted at all compartments with MCT being the prevailing type in bronchi, bronchioles and the alveolar parenchyma. MCTC were more ...

T cell mediated immune responses in the gut can produce enteropathy and malabsorption. We have investigated the relevance of mucosal mast cells (MMC) to the mechanisms of this enteropathy by using graft-versus-host reaction (GvHR) in the rat as a model of mucosal delayed type hypersensitivity. Measurements of mucosal architecture, intraepithelial lymphocytes (IEL) and MMC counts were performed in control and experimental rats, and release of rat mast cell protease II (RMCPII) into the bloodstream was used as an index of MMC activation. In unirradiated rats, jejunal MMC count was increased on day 14 of the GvHR (mean 272/mm2 v 182 in controls, p less than 0.01), as was serum RMCPII (p less than 0.01). Irradiated rats (4.5 Gy, reconstituted with isogeneic spleen cells) had low counts of IEL and crypt hyperplasia seven to 14 days after irradiation. Irradiated rats with GvHR (induced by ip injection of parental strain spleen cells) and studied on days 7, 10 and 14, had significant enteropathy with ...

Mast cells are found in tissues throughout the body where they play important roles in the regulation of inflammatory responses. One characteristic feature of mast cells is their longevity. Although it is well established that mast cell survival is dependent on stem cell factor (SCF), it has not been described how this process is regulated. Herein, we report that SCF promotes mast cell survival through inactivation of the Forkhead transcription factor FOXO3a (forkhead box, class O3A) and down-regulation and phosphorylation of its target Bim (Bcl-2 [B-cell lymphoma-2] interacting modulator of cell death), a Bcl-2 homology 3 (BH3)-only proapoptotic protein. SCF induced a rapid and transient phosphorylation of Akt (protein kinase B) and FOXO3a. SCF treatment prevented up-regulation of Bim protein expression and led to increased Bim phosphorylation. Bim phosphorylation was inhibited by PD98059 and LY294002 treatment, suggesting the involvement of mitogen-activated protein kinase ...

Our mast cell degranulation results are in accordance with other studies. Levy et al. 3showed that vancomycin induced 22.9% histamine release. Benyon et al. 23showed that calcium ionophore A23187 released 28.6% histamine. Stellato et al. 5showed a significant positive correlation between the percentages of histamine and tryptase release induced by morphine from human skin mast cells, and the release was calcium dependent, and, as in our study, no release was observed if calcium was removed from the incubation buffer. 13Atracurium is a known histamine releaser, both in vivo 24and in vitro (net histamine release 12% with 10−3M), 6although another study reports that atracurium causes modest histamine release. 25We also found only a modest release of histamine and tryptase after incubation with atracurium. Tryptase has been shown to be released with histamine from human heart and synovial mast cells, if stimulated immunologically in vitro , 26,27and others have shown that it is released with ...

TY - JOUR. T1 - Multifunctional cytokine expression by human mast cells. T2 - Regulation by T cell membrane contact and glucocorticoids. AU - Krishnaswamy, G.. AU - Lakshman, T.. AU - Miller, A. R.. AU - Srikanth, S.. AU - Hall, K.. AU - Huang, S. K.. AU - Suttles, J.. AU - Smith, J. K.. AU - Stout, R.. PY - 1997/3. Y1 - 1997/3. N2 - Human mast cells readily release a variety of mediators, including cytokines, in response to IgE receptor crosslinking, but the mechanisms governing the expression of cytokines are still unclear. Using a human mast cell line, HMC-I, we show expression of cytokine transcripts as early as 2 h after activation with ionomycin and phorbol myristate acetate (PMA). Resting HMC-I cells expressed transcripts for interleukin-1 receptor antagonist (IL- IRA), IL-2, IL-4, IL-5, GM-CSF, and weakly for IL-8, and stimulation with ionomycin and PMA induced additional transcripts for IL-6 and IL-13 and upregulated expression of IL-8 transcripts. HMC1 cells secreted IL-4, IL-8, and ...

METHODS AND RESULTS Specimens of normal and atherosclerotic human coronary intima from 32 autopsy cases with ages ranging from 13 to 67 years were stained with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase. Of the tryptase-containing mast cells, a variable proportion (average, 40%; range, 0% to 100%) also contained chymase. In the normal coronary intimas, mast cells amounted to 0.1% of all nucleated cells. In the fatty streaks, this proportion was higher by 9-fold, and in the cap, core, and shoulder regions of atheromas by 5-, 5-, and 10-fold, respectively. Electron and light microscopic studies of mast cells in the shoulder region of atheromas revealed degranulation of mast cells, a sign of their activation, and moreover, that the proportion of activated mast cells was much higher (85%) in this region than in the normal intima (18%). ...

Mast cells are abundantly expressed in synovial tissues and have been proposed to exert proinflammatory effects primarily based on antibody transfer-induced disease models (28, 29). The mode of mast cell activation and the mechanism by which activated-mast cells mediate antigen-induced arthritis are largely unknown and likely complex. We now provide direct in vivo evidence that IL-33 plays a major role in mast cell activation in the context of antigen-induced arthritis. Thus, IL-33 enhanced CIA when ST2−/− mice were reconstituted with BMMCs from WT but not from ST2−/− mice (Fig. 5). Our data also provide mechanisms by which mast cells could promote inflammatory synovitis (Fig. 6). IL-33 induces mast cell production of IL-1, IL-6, IL-13, and a range of chemokines (13, 14, 30) (Fig. 4). Because both IL-1 and IL-6 play crucial roles in the induction of Th17 cells (31-33), a key pathogenic cell type in arthritis (21, 22), our studies indicate a relationship between ST2/IL-33 function and ...

The mast cell possesses within itself granules of especially inflammatory biochemicals meant for use against invading parasites. (Think of these as small bombs that can be released). The mast cell has binding sites on its surface for a special type of antibody called IgE. IgE is produced in response to exposure to antigens typical of parasites (i.e., worm skin proteins, or similarly shaped proteins). IgE antibodies, which are shaped like tiny Ys, find their way to a tissue mast cell and perch there. With enough exposure to the antigen in question, the mast cell may be covered with Y- shaped IgE antibodies like the fluff of a dandelion. The mast cell is said, at this point, to be sensitized ...

The mast cell possesses within itself granules of especially inflammatory biochemicals meant for use against invading parasites. (Think of these as small bombs that can be released). The mast cell has binding sites on its surface for a special type of antibody called IgE. IgE is produced in response to exposure to antigens typical of parasites (i.e., worm skin proteins, or similarly shaped proteins). IgE antibodies, which are shaped like tiny Ys, find their way to a tissue mast cell and perch there. With enough exposure to the antigen in question, the mast cell may be covered with Y- shaped IgE antibodies like the fluff of a dandelion. The mast cell is said, at this point, to be sensitized ...

TY - JOUR. T1 - ATP-induced pore formation in the plasma membrane of rat peritoneal mast cells. AU - Hofmann, Polly. AU - Metzger, Joseph M.. AU - Greaser, Marion L.. AU - Moss, Richard L.. PY - 1990/3/1. Y1 - 1990/3/1. N2 - Various functional roles for myosin light chain 2 (LC2) have been suggested on the basis of numerous and predominantly in vitro biochemical studies. Using skinned fibers from rabbit psoas muscle, the present study examines the influence of partial removal of LC2 on isometric tension, stiffness, and maximum velocity of shortening at various levels of activation by Ca2+. Isometric tension, stiffness, and velocity of shortening were measured at pCa values between 6.6 and 4.5 (a) in a control fiber segment, (b) in the same fiber segment after partial removal of LC2, and (c) after recombination with LC2. The extraction solution contained 20 mM EDTA, 20 or 50 mM KC1, and either imidazole or PO4 2− as a pH buffer (pH 7.0). The amount of LC2 extracted varied with the temperature, ...

The nonselective beta-adrenoceptor agonist, isoprenaline (pD2; 8.8 +/- 0.2), and selective beta2-adrenoceptor agonists, clenbuterol (9.2 +/- 0.4) and salbutamol (7.1 +/- 0.1), inhibited the immunoglobulin E-mediated release of histamine from human lung mast cells in a concentration-dependent manner. …

Mast cell activation disease is used here as an umbrella term that includes both MCAS and SM. Mast cell activation disease is diagnosed if both major criteria, or one major criterion and one minor criterion, are present. Following the diagnosis with mast cell activation disease, a bone marrow biopsy is used to narrow the diagnosis down to either SM or MCAS.. Major criteria:. - Multifocal of disseminated dense infiltrates of mast cells in bone marrow biopsies and/or in sections of other extracutaneous organ(s) (GI tract biopsies; CD117-, tryptase- and CD25- stained). - Unique constellation of clinical complaints as a result of a pathologically increased mast cell activity (mast cell mediator release symptom). Minor criteria:. - Mast cells in bone marrow or other extracutaneous organ(s) show an abnormal morphology (,25%) in bone marrow smears or in histologies. - Mast cells in bone marrow express CD2 and/or CD25. - Detection of genetic changes in mast cells from blood, bone marrow or ...

TY - JOUR. T1 - Mechanism of bradykinin-induced histamine release from rat peritoneal mast cells. AU - Zhao, Qiu E.. AU - Mihara, Takuma. AU - Sugimoto, Yukio. AU - Kamei, Chiaki. PY - 1996/2. Y1 - 1996/2. N2 - Bradykinin at concentrations higher than 2 μM caused a significant histamine release from rat peritoneal mast cells when extracellular Ca2+ was removed from the medium. Under the same experimental conditions, bradykinin increased Ca2+ release from the intracellular Ca store of the rat peritoneal mast cells, and a clear relationship was observed between the magnitude of histamine release and an increase in fluorescence intensity. Addition of Ca2+ to the medium resulted in an inhibition of the response to bradykinin in a concentration-dependent manner. Almost the same results were obtained when Mg2+, Ba2+ and La3+ were added to the medium. Neither B1 nor B2 antagonists caused significant antagonistic effects on histamine release induced by bradykinin. However, B2 antagonists caused a ...

Immune cells like NK cells, T cells, neutrophils and mast cells store high amounts of granule serine proteases, graspases. Graspases are encoded from the mast cell chymase locus. The human locus holds four genes: α-chymase, cathepsin G, and granzymes H and B. In contrast, the mouse locus contains at least 14 genes. Many of these belong to subfamilies not found in human, e.g. the Mcpt8-family. These differences hamper functional comparisons of graspases and of immune cells in the two species. Studies of the mast cell chymase locus are therefore important to better understand the mammalian immune system. In this thesis, the evolution of the mast cell chymase locus was analysed by mapping the locus in all available mammalian genome sequences. It was revealed that one single ancestral gene founded this locus probably over 215 million years ago. This ancestor was duplicated more than 185 million years ago. One copy evolved into the α-chymases, whereas the second copy founded the families of ...

Mouse mast cell protease-4 (mMCP-4) has been associated with autoimmune and inflammatory illnesses although the precise systems underlying its function in these pathological circumstances remain unclear. impaired in cultured mMCP-4?/? MCs and in your skin of pathogenic IgG-injected mMCP-4?/? mice. MMP-9 activation had not been AS-252424 completely restored by regional reconstitution with WT or mMCP-4?/? PMNs. Local reconstitution with mMCP-4+/+ MCs but not with mMCP-4?/? MCs restored blistering MMP-9 activation and PMN recruitment in mMCP-4?/? mice. mMCP-4 also degraded the hemidesmosomal transmembrane protein BP180 AS-252424 both in the skin and (1% 1 cm) = 13.6). The titers of anti-murine BP180 antibodies in both the unfractionated rabbit serum and in the purified IgG portion were assayed by indirect immunofluorescence (IF) using mouse pores and skin cryosections as substrate. The antibody preparations were also tested by immunoblotting against the GST-mBP180ABC fusion protein. The IF and ...

The acidic granules of natural killer (NK) cells, T cells, mast cells, and neutrophils store large amounts of serine proteases. Functionally, these proteases are involved, e.g., in the induction of apoptosis, the recruitment of inflammatory cells, and the remodeling of extra-cellular matrix. Among the granule proteases are the phylogenetically related mast cell chymases, neutrophil cathepsin G, and T-cell granzymes (Gzm B to H and Gzm N), which share the characteristic absence of a Cys191-Cys220 bridge. The genes of these proteases are clustered in one locus, the mast cell chymase locus, in all previously investigated mammals. In this paper, we present a detailed analysis of the chymase locus in cattle (Bos taurus) and opossum (Monodelphis domestica). The gained information delineates the evolution of the chymase locus over more than 200 million years. Surprisingly, the cattle chymase locus contains two α-chymase and two cathepsin G genes where all other studied chymase loci have single genes. ...

Mast cells are responsible for the majority of allergic conditions. It was originally thought that almost all allergic events were mediated directly only via the high-affinity immunoglobulin E receptors. However, recent evidence showed that many other receptors, such as G protein-coupled receptors and ligand-gated ion channels, are also directly involved in mast cell degranulation, the release of inflammatory mediators such as histamine, serine proteases, leukotrienes, heparin, and serotonin. These mediators are responsible for the symptoms in allergic conditions such as allergic asthma. In recent years, it has been realized that purinergic signaling, induced via the activation of G protein-coupled adenosine receptors and P2Y nucleotide receptors, as well as by ATP-gated P2X receptors, plays a significant role in mast cell degranulation. Both adenosine and ATP can induce degranulation and bronchoconstriction on their own and synergistically with allergens. All three classes of receptors, adenosine, P2X

TY - JOUR. T1 - Role of mast cells and their mediators in failing myocardium under mechanical ventricular support. AU - Akgul, Ahmet. AU - Skrabal, Christian A.. AU - Thompson, Larry O.. AU - Loebe, Matthias. AU - Lafuente, Javier A.. AU - Noon, George P.. AU - Youker, Keith A.. PY - 2004/6/1. Y1 - 2004/6/1. N2 - Background Mast cells have been implicated in tissue remodeling and fibroblast stimulation. We explored the effect of mechanical support by left ventricular assist device (LVAD) in failing myocardium and looked into grade and distribution of interstitial fibrosis, mast cell density, mast cell phenotypes and basic fibroblast growth factor (bFGF) expression pre- and post-LVAD. Methods Myocardial tissue was obtained from 20 patients with end-stage cardiomyopathy at the time of LVAD implantation and LVAD removal and from 7 donor hearts not used for transplantation. Tissue sections were stained for mast cells using tryptase as a marker and the myocardial fibrosis was measured. Double ...

To gain insight into the biological role of mast cell chymase we have generated a mouse strain with a targeted deletion in the gene for mast cell protease 4 (mMCP-4), the mouse chymase that has the closest relationship to the human chymase in terms of tissue localization and functional properties. reactions (22), and angiogenesis in hamster sponge granulomas (23). It is important to stress that although the reports described above provide evidence for an involvement of chymases in various pathological conditions, the exact mode of action for chymase has not been determined, i.e., the in vivo substrates for chymases have not been identified. Further, limited knowledge is available as regards the individual contribution of the various MC chymases. To gain further insight into the biological role of MC chymase we have here inactivated the gene for mMCP-4. Materials and Methods Reagents. The chromogenic peptide substrates S-2586, S-2238 and S-2288 were from Chromogenix. The CPA substrate M-2245 ...

Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG(35-55) plus complete Freunds adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE ...

Concern about the use of nanomaterials has increased significantly in recent years due to potentially hazardous impacts on human health. Mast cells are critical for innate and adaptive immune responses, often modulating allergic and pathogenic conditions. Mast cells are well known to act in response to danger signals through a variety of receptors and pathways including IL-33 and the IL-1-like receptor ST2. Here, the involvement of mast cells and the IL-33/ST2 axis in pulmonary and cardiovascular responses to multi-walled carbon nanotube (MWCNT) exposure are examined. Toxicological effects of MWCNTs are observed only in mice with a sufficient population of mast cells and are not observed when mast cells are absent or incapable of responding to IL-33. Our findings establish for the first time that mast cells and the IL-33/ST2 axis orchestrates adverse pulmonary and cardiovascular responses to an engineered nanomaterial, giving insight into a previously unknown mechanism of toxicity. This novel mechanism

Primary graft dysfunction (PGD), as characterized by pulmonary infiltrates and high oxygen requirements shortly after reperfusion, is the major cause of early morbidity and mortality after lung transplantation. Donor, recipient and allograft-handling factors are thought to contribute, although new insights regarding pathogenesis are needed to guide approaches to prevention and therapy. Mast cells have been implicated in ischemic tissue injury in other model systems and in allograft rejection, leading to the hypothesis that mast cell degranulation contributes to lung injury following reperfusion injury. We tested this hypothesis in a mouse model of PGD involving reversible disruption of blood flow to one lung. Metrics of injury included albumin permeability, plasma extravasation, lung histopathology, and mast cell degranulation. Responses were assessed in wild-type (Kit +/+ ) and mast cell-deficient (Kit W-sh/W-sh ) mice. Because mouse

TY - JOUR. T1 - Effective mast cell degranulating peptide inhibitors of the IgE/FcεRI receptor interaction. AU - Buku, Angeliki. AU - Keselman, Inna. AU - Lupyan, Dmitry. AU - Mezei, Mihaly. AU - Price, Joseph. PY - 2008/8/1. Y1 - 2008/8/1. N2 - Previous studies with mast cell degranulating (MCD) peptide have shown that peptide [Ala12]MCD 8 was an inhibitor of IgE binding to mast cell receptors. In an attempt to produce increased inhibition, analogs were synthesized that maintained the alanine residue in position 12 in the MCD peptide sequence and were further modified at both termini. Analogs modified at the C-terminus were [Ala12,desLys21]MCD 2 and [Ala 12,d-Lys21]MCD 4. N-terminus modifications were [desLys6-Arg7-His8,Ala12]MCD 1, [Ala6, Ala12]MCD 6, and [Val6,Ala 12]MCD 7. To assess the role of the Proline12, analogs [d-Ala12]MCD 3 and [Meleu12]MCD 5 were also synthesized. The analogs were tested for binding to the IgE receptor in cultured mast cells. Inhibitory activity of IgE-caused ...

Muscle layer alterations such as myositis and fibrosis that could contribute to the pathogenesis of Chagas disease megas are often found both in the esophagus1 3 16 and in the colon2 16. According to Tafuri and Raso16, fibrosis in Chagas megaesophagus sometimes is focal, possibly representing a sequel of myositis and thought to be associated with mast cell infiltrate, and sometimes is diffuse and interstitial without showing a topographic relationship with the inflammation. Andrade & Andrade8, analyzing myocardial fibrosis, also accepted that focal fibrosis could result from scarring of inflammatory foci related to the presence of mast cells. Nonetheless, Andrade & Andrade8 stressed that the pathogenesis of diffuse interstitial fibrosis had not been clarified.. Quantitative studies made on cardiopathic Chagas disease patients7 and on the circular esophagus musculature of chronic Chagas patients without megaesophagus11, have reported a marked increase in the mast cell count in these organs. ...

TY - JOUR. T1 - Ultrastructural immunolocalization of basic fibroblast growth factor in mast cell secretory granules. T2 - Morphological evidence for bFGF release through degranulation. AU - Qu, Zhenhong. AU - Kayton, Robert J.. AU - Ahmadi, Proochista. AU - Liebler, Janice M.. AU - Powers, Michael R.. AU - Planck, Stephen R.. AU - Rosenbaum, James T.. PY - 1998/10. Y1 - 1998/10. N2 - We previously reported that mast cells (MCs) serve as a source of basic fibroblast growth factor (bFGF), a potent angiogenic and mitogenic polypeptide, suggesting that bFGF may mediate MC-related neovascularization and fibroproliferation. Unlike many other growth factors, bFGF lacks a classic peptide sequence for its secretion, and the mechanism(s) for its release remains controversial. Because MCs release a wide spectrum of bioactive products via degranulation, we hypothesized that MC degranulation may be a mechanism of bFGF release and used ultrastructural immunohistochemistry to test the hypothesis. We reasoned ...

It has been suggested that histamine plays an important role in the pathogenesis of cluster headache. In addition, both neurogenic and vascular components have been described during cluster headache attacks without an obvious anatomical link between them. Our ultrastructural observations of human temporal arteries from cluster headache patients and their comparison to those from a control group strongly suggest that mast cells may be this link. Mast cells in both groups show a very close apposition with nerve fibres, suggesting a functional interaction between them. Moreover, in the cluster headache group exclusively, adventitial mast cells show profound morphological modifications suggesting progressive degranulation. These data strongly suggest that mast cells could be directly or indirectly involved in the pathophysiology of cluster headaches. ...

Converging sources of evidence point to a role for inflammation in the development of depression, fatigue and cognitive dysfunction. More precisely, the tryptophan (TRP) catabolism is thought to play a major role in inflammation-induced depression. Mastocytosis is a rare disease in which chronic symptoms, including depression, are related to mast cell accumulation and activation. Our objectives were to study the correlations between neuropsychiatric features and the TRP catabolism pathway in mastocytosis in order to demonstrate mast cells potential involvement in inflammation-induced depression. Fifty-four patients with mastocytosis and a mean age of 50.1 years were enrolled in the study and compared healthy age-matched controls. Depression and stress were evaluated with the Beck Depression Inventory revised and the Perceived Stress Scale. All patients had measurements of TRP, serotonin (5-HT), kynurenine (KYN), indoleamine 2,3-dioxygenase 1 (IDO1) activity (ratio KYN/TRP), kynurenic acid (KA) ...

35. Why are there different sets of criteria for mast cell activation syndrome? What are the differences between them?. To answer this fully, we need to first discuss the history behind some terms.. Mast cell activation syndrome was first used to describe episodes of mast cell mediator release symptoms in a paper published in 2007 (Akin 2007). Specifically, the term was used to detail the experience of patients who had symptoms we commonly associated with mast cell activation, like flushing, hives, and low blood pressure.. However, the patients in this study were all found to have some features of systemic mastocytosis. While they had some of the criteria for an SM diagnosis, they didnt meet all the criteria. These patients sort of looked like SM and quacked like SM but would not cleanly meet the diagnostic criteria. So the author of that paper made a separate diagnostic category for them. He called it monoclonal mast cell activation syndrome.. The use of the word monoclonal is VERY important ...

TY - JOUR. T1 - Heterogeneity of human basophils and mast cells in response to muscle relaxants. AU - Stellato, C.. AU - de Paulis, A.. AU - de Crescenzo, G.. AU - Tatangelo, F.. AU - Rickler, O.. AU - Marone, G.. PY - 1992/6. Y1 - 1992/6. N2 - We investigated the in vitro effects of increasing concentrations (10-5-10-3M) of four muscle relaxants (succinylcholine, d-tubocurarine, vecuronium and atracurium) on histamine release (HR) from human peripheral blood basophils and mast cells isolated from lung parenchyma (HLMC) and skin tissues (HSMC). Basophils released less than 5% of their histamine content when incubated with any one of the muscle relaxants. In contrast, mast cells showed a marked heterogeneity in their response. Succinylcholine did not induce HR from any type of mast cell, and only high concentrations of d-tubocurarine (10-3M) caused HR from HSMC and HLMC. Vecuronium concentration-dependently induced HR from HLMC and HSMC. Atracurium concentration-dependently caused marked HR from ...

MONOSAN item MON8101 Mouse anti Mast Cell Chymase, clone CC1 (Monoclonal), 100 ug. Contact us for more information about item MON8101.

Mastocytosis: A disease of Mast Cells. What are Mast Cells ?. Mast cells belong to the family of ´white blood cells´ most of which are produced in our bone marrow. The mast cell was first discovered and described by Paul Ehrlich in 1876. In contrast to most other bone marrow-derived cells, mast cells are not found in the peripheral blood, but are located in the tissues where they reside for many months or even years. Like most white blood cells, mast cells belong to the immune system that helps in the body´s defence against bacteria and other microbes. As part of an alarm system, mast cells can respond very rapidly to foreign attacks of microbes by releasing potent vasoactive and defence-related molecules into the tissues in local areas. These chemical mediators are released from mast cells systemically in our body during a severe allergic reaction which may result in the clinical picture of anaphylaxis. One of the most important chemical mediators of mast cells is histamine, which can cause ...

In this issue of the International Neurourology Journal, we have published an article reviewing new perspectives on mast cell regulation [4]. It was confirmed in other organs that interleukin (IL) 33 can modulate allergic inflammation. IL-33 is closely related to mast cell activation, which is considered the core of IC pathogenesis. Therefore, it may be possible to regulate mast cell activation by inhibiting IL-33. Promising results have been reported in a number of studies. However, because the reaction of the anti-IL-33 could vary in different organs, we have many challenges to overcome before systemic administration of anti-IL-33 as a therapeutic agent can be implemented. Nevertheless, this is valuable work as it presents a potential therapeutic target for an incurable disease yet unconquered by modern medicine ...

In 2008 Dr. Afrin started coming to understand that a newly recognized type of mast cell disease, now called mast cell activation syndrome (MCAS), was the underlying diagnosis in many patients he was seeing who were each suffering large assortments - quite different from one patient to the next - of chronic multisystem inflammatory illnesses of unclear cause. Dr. Afrin soon gained experience that MCAS is far more prevalent than the only mast cell disease previously known to medicine (the rare disease of mastocytosis) and that most MCAS patients, once accurately diagnosed, can eventually find significantly helpful medications targeted at the disease. The frequency and magnitude of the improvements Dr. Afrin has seen - even the relief that comes from finally having a unifying diagnosis other than psychosomatism - have spurred him to focus in this area, not only tending to the needs of his patients but also pursuing research to advance our understanding of the disease and helping to educate other ...

In 2008 Dr. Afrin started coming to understand that a newly recognized type of mast cell disease, now called mast cell activation syndrome (MCAS), was the underlying diagnosis in many patients he was seeing who were each suffering large assortments - quite different from one patient to the next - of chronic multisystem inflammatory illnesses of unclear cause. Dr. Afrin soon gained experience that MCAS is far more prevalent than the only mast cell disease previously known to medicine (the rare disease of mastocytosis) and that most MCAS patients, once accurately diagnosed, can eventually find significantly helpful medications targeted at the disease. The frequency and magnitude of the improvements Dr. Afrin has seen - even the relief that comes from finally having a unifying diagnosis other than psychosomatism - have spurred him to focus in this area, not only tending to the needs of his patients but also pursuing research to advance our understanding of the disease and helping to educate other ...

Mast cell activation initiated by antigen-mediated crosslinking of IgE receptors results in stimulated exocytosis of secretory lysosomes in the process known as degranulation. Much has been learned about the molecular mechanisms important for this process, including the critical role of Ca2+ mobilization, but spatio-temporal relationships between stimulated Ca2+ mobilization and granule exocytosis are incompletely understood. Here we use a novel imaging-based method that utilizes fluorescein isothiocyanate (FITC)-dextran as a reporter for granule exocytosis in RBL mast cells and takes advantage of the pH sensitivity of FITC. We demonstrate the selectivity of FITC-dextran, accumulated by fluid phase uptake, as a marker for secretory lysosomes, and we characterize its capacity to delineate different exocytotic events, including full fusion, kiss-and-run transient fusion, and compound exocytosis. Using this method, we find strong dependence of degranulation kinetics on the duration of ...

Im trying to culture rat BMMCs (from Brown Norway rats) using similar culture conditions to those weve used successfully with mouse BMMCs, but with no luck. My current media is pretty standard - RPMI, b-ME, 10% FBS, P/S/glut, sodium pyruvate. rrIl-3 added fresh, tested with and without rSCF. also tested ConA stimulated spleen conditioned media, as a source of IL-3, but my cells seemed to stick to the plate and die faster than previous cultures. I only change out half the media with each feeding, as with mouse BMMCs or the viability decreases. Very few problems with viability - routinely ,90% even after 35 days in culture. My main problem is that all of my cells keep adhering to the plastic - ive looked at the adherent cells by flow and spun some out onto slides and they appear to be monocytes / macs, which i dont want. All the suspension cells dwindle away quite quickly ...

Other names: mast cell protease I; skeletal muscle protease; skin chymotryptic proteinase; mast cell serine proteinase, chymase; skeletal muscle (SK) protease. Comments: In mast cell granules. In peptidase family S1 (trypsin family). Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 97501-92-3. References 1. Woodbury, R.G., Everitt, M. and Neurath, H. Mast cell proteases. Methods Enzymol. 80 (1981) 588-609. [PMID: 7043202]. 2. Powers, J.C., Tanaka, T., Harper, J.W., Minematsu, Y., Barker, L., Lincoln, D., Crumley, K.V., Fraki, J.E., Schechter, N.M., Lazarus, G.G., Nakajima, K., Nakashino, K., Neurath, H. and Woodbury, R.G. Mammalian chymotrypsin-like enzymes. Comparative reactivities of rat mast cell proteases, human and dog skin chymases, and human cathepsin G with peptide 4-nitroanilide substrates and with peptide chloromethyl ketone and sulfonyl fluoride inhibitors. Biochemistry 24 (1985) 2048-2058. [PMID: 3893542]. 3. Johnson, L.A., Moon, K.E. and ...

Our results clearly demonstrate that acute psychological stress induces cardiac mast cell degranulation in 30 min through the local release of CRH, since anti-CRH serum or affinity purified antibody to CRH could neutralize this effect. The same antiserum to CRH used here had previously been shown to block carrageenin-induced skin inflammation (Karalis et al., 1991) and stress-induced dura mast cell degranulation (Theoharides et al., 1995). Pretreatment with the CRHR-1 selective antagonist Antalarmin partially reduced stress-induced mast cell degranulation, implying that CRH receptors are involved. This finding is supported by the fact that CRH receptor mRNA was shown to be expressed in mouse heart (Stenzelet al., 1995). Direct CRHR-mediated mast cell degranulation has recently been demonstrated in rat skin although human leukemic mast cells were shown to express mRNA for CRHR1 (Theoharideset al., 1998). The fact that antalarmin was only a weak inhibitor may be due to its poor solubility or the ...

Upon dermal vibration, patients with vibratory urticaria (VU) experience localized hives and increased histamine levels in serum. These responses are caused by hyperreactivity of skin mast cells to a mechanical stimulus. We found that patients with a familial form of VU harbor a missense substitution in an adhesion G-protein coupled receptor (aGPCR), ADGRE2, that renders mast cells more susceptible to vibration-induced activation. However, the mechanisms of activation of ADGRE2 and how this mutation enhances the ability of mast cells to respond to a mechanical stimulus is not understood. In the present study, we detail the signaling pathways activated through the ADGRE2 receptor upon ligand binding and vibration. Our results provide insights into the structural requirements for ADGE2 activation, how it signals and possible therapeutic targets for patients with VU.. ...

Mast cells are present in the blood, bone marrow and various tissues throughout the body. They originally arise from the bone marrow and migrate to other areas as needed. Rat studies have previously confirmed that stress increases mast cells in the intestine and causes leaky gut. Mast cells seem to have several important functions in the gut including not only immune function but also gut nerve function. Mast cell activation can result in increase gut contractions or decrease gut contractions. A recent study confirms that the stress hormone corticotropin-releasing hormone (CRH) stimulates mast cells in the human colon through receptors present on the mast cells and can trigger their release of chemicals from granules. Increase mast cells are found in association with other inflammatory bowel diseases such as ulcerative colitis and Crohns disease as well as in celiac disease, allergic esophagus or eosinophilic esophagitis, and in post-infectious irritable bowel syndrome (IBS). Mast cells are ...

Ive been debating doing a month summary for all my doctor visits. Nothing detailed. Types of doctors seen and status of visit. Follow-up, new patient, etc. Im leaning towards doing this even though its a lot of work and being this sick is a job enough already. Ive also decided to try keeping a log of my mast cell explosion episodes since starting Xolair and understanding mast cell activation disease (or syndrome) better. Its so damned aggravating that the most information about MCAS on the internet comes from patients. For the Mast cell degranulation attacks (because I think thats probably the best description) Ill note what I assume are triggers, times, meds, and ALL symptoms. If youre reading this, what would you like to hear about?. ...

Only recently recognised, mast cell activation syndrome (MCAS) is a large, prevalent collection of illnesses resulting from mast cells (MCs) which are inappropriately activated but which, in contrast to the (collectively rare) forms of mastocytosis, are not significantly proliferating. Due to the diversity of direct and indirect, local and remote effects of the menagerie of mediators released by MCs, likely due to highly heterogeneous sets of mutations in MC regulatory elements, MCAS typically presents as chronic, persistent or recurrent, waxing/waning or slowly progressive, generally inflammatory multisystem polymorbidity. Initial manifestations often occur in childhood but are non-specific; in fact, virtually all of the syndromes manifestations are non-specific, leading to decades of mysterious illness complicated by incorrect or superficial diagnoses often poorly responsive to empiric therapies. Diagnosis is further challenged in detecting specific biomarkers of MC activation other than ...

TY - JOUR. T1 - FcεRI Signaling in the Modulation of Allergic Response. T2 - Role of Mast Cell-Derived Exosomes. AU - Lecce, Mario. AU - Molfetta, Rosa. AU - Milito, Nadia Domenica. AU - Santoni, Angela. AU - Paolini, Rossella. PY - 2020/7/30. Y1 - 2020/7/30. N2 - Mast cells (MCs) are immune cells that act as environment resident sentinels playing a crucial role in Th2-mediated immune responses, including allergic reactions. Distinguishing features of MCs are the presence of numerous cytoplasmic granules that encapsulate a wide array of preformed bio-active molecules and the constitutive expression of the high affinity receptor of IgE (FcεRI). Upon FcεRI engagement by means of IgE and multivalent antigens, aggregated receptors trigger biochemical pathways that ultimately lead to the release of granule-stored and newly synthesized pro-inflammatory mediators. Additionally, MCs are also able to release exosomes either constitutively or upon stimulation. Exosomes are nanosized vesicles of ...

Mast cells are cells that reside in the connective tissues, especially those vessels and nerves that are closest to the external surfaces (e.g., skin, lungs, nose, mouth). Their primary functions include defense against parasitic infestations, tissue repair, and the formation of new blood vessels (angiogenesis). A tumor consisting of mast cells is called a mastocytoma, or mast cell tumor.

Mast cell degranulation, the release of allergic mediators, is important in allergy, asthma, and parasite defense. Here we demonstrate...

TY - JOUR. T1 - Glycomic analysis of human mast cells, eosinophils and basophils. AU - North, Simon J.. AU - Von Gunten, Stephan. AU - Antonopoulos, Aristotelis. AU - Trollope, Alana. AU - MacGlashan, Donald W.. AU - Jang-Lee, Jihye. AU - Dell, Anne. AU - Metcalfe, Dean D.. AU - Kirshenbaum, Arnold S.. AU - Bochner, Bruce S.. AU - Haslam, Stuart M.. N1 - Funding Information: This work was supported by the Analytical Glycotechnology Core (Core C) of the Consortium for Functional Glycomics (GM 62116), the Swiss National Foundation (PBBEB-113394 to S.G.), the National Institutes of Health (AI 72265 to B.S.B.). PY - 2012/1. Y1 - 2012/1. N2 - In allergic diseases such as asthma, eosinophils, basophils and mast cells, through release of preformed and newly generated mediators, granule proteins and cytokines, are recognized as key effector cells. While their surface protein phenotypes, mediator release profiles, ontogeny, cell trafficking and genomes have been generally explored and compared, there has ...

wrote: Hi Histonetters, I was wondering if anyone knows how to stain paraffin-embedded tissues for a certain Ab (standard IHC), and use toluidine blue to stain mast cells on the same section. Is it at all possible? I emphasize that I would like to use toluidine blue not for counterstaining, but to detect mast cells, and to still be able to see my IHC staining. Glad to recieve any piece of advice. Thanks, Moran -- Moran Elishmereni Department of Pharmacology and Experimental Therapeutics School of Pharmacy, Faculty of Medicine The Hebrew University of Jerusalem POB 12065 Jerusalem 91120, ISRAEL Tel: 972-2-675-8746 Fax: 972-2-675-8144 Email: [email protected] _______________________________________________ Histonet mailing list [email protected] http://lists.utsouthwestern.edu/mailman/listinfo/histonet --------------------------------- Be a better Globetrotter. Get better travel answers from someone who knows. Yahoo! Answers - Check it out. ...

In summary, I would favor catamenial anaphylaxis and not autoimmune progesterone dermatitis, idiopathic anaphylaxis, mast cell disorder or NSAID induced anaphylaxis.. I recently had an exchange with a lovely young woman who found out her mast cell flares during menstruation were kept completely at bay after receiving a diagnosis of catamenial epilepsy and being put on the proper medicines for that condition. I found that extremely interesting so Ill be doing more research into this and will be writing on it in a future post.. As for those of us with definite mast cell disorders who struggle each month through ovulation and menstruation, we have few options. Hormone therapy generally makes us worse so increasing our doses of regular meds or even relying on rescue meds are our main options. For some of us, having a hysterectomy (or oophorectomy) may be the only thing that stops the female cycle MCAS flares but unfortunately, in some cases, it can also trigger us.. There are no easy ...

Mast cells participate in allergy and inflammation by secreting inflammatory mediators such as histamine and proinflammatory cytokines. Flavonoids are naturally occurring molecules with antioxidant, cytoprotective, and antiinflammatory actions. However, effect of flavonoids on the release of histamine and proinflammatory mediator, and their comparative mechanism of action in mast cells were not well defined. Here, we compared the effect of six flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) on the mast cell-mediated allergic inflammation. Fisetin, kaempferol, myricetin, quercetin, and rutin inhibited IgE or phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PMACI)-mediated histamine release in RBL-2H3 cells. These five flavonoids also inhibited elevation of intracellular calcium. Gene expressions and secretion of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 were assessed in PMACI-stimulated ...

TY - JOUR. T1 - Inhibitor effect of antioxidant flavonoids quercitin and capsaicin in mast cell inflammation. AU - Pandolfi, Franco. AU - Shaik-Dasthagirisaheb, Y. B.. AU - Varvara, G.. AU - Murmura, G.. AU - Saggini, A.. AU - Caraffa, A.. AU - Antinolfi, P.. AU - Tetè, S.. AU - Rosati, M.. AU - Cianchetti, E.. AU - Toniato, E.. AU - Speranza, L.. AU - Pantalone, A.. AU - Saggini, R.. AU - Di Tommaso, L. M.. AU - Conti, P.. AU - Theoharides, T. C.. PY - 2013. Y1 - 2013. N2 - Mast cells are essential not only for allergies but also for innate and acquired immunity, autoimmunity and inflammation, and they are recognized as a new type of immunoregulatory cells capable of producing different cytokines. Natural compounds have long been recognized to possess anti-inflammatory, antioxidant and anticancergenic activity. Quercitin is an inhibitor for mast cells and is a potent antioxidant, cytoprotective and anti-inflammatory compound and has a negative effect on intracellular regulator signal events ...

Proteomic-based drug testing is an emerging approach to establish the clinical value and anti-neoplastic potential of multikinase inhibitors. The multikinase inhibitor midostaurin (PKC412) is a promising new agent used to treat patients with advanced systemic mastocytosis (SM). We examined the target interaction profiles and the mast cell (MC)-targeting effects of two pharmacologically relevant midostaurin metabolites, CGP52421 and CGP62221. All three compounds, midostaurin and the two metabolites, suppressed IgE-dependent histamine secretion in basophils and MC with reasonable IC50 values. Midostaurin and CGP62221 also produced growth inhibition and dephosphorylation of KIT in the MC leukemia cell line HMC-1.2, whereas the second metabolite, CGP52421, which accumulates in vivo, showed no substantial effects. Chemical proteomic profiling and drug competition experiments revealed that midostaurin interacts with KIT and several additional kinase targets. The key downstream regulator FES was recognized by

OMALIZUMAB TRIAL. The results of the first of three phase III clinical trials of the effects of omalizumab in patients with chronic idiopathic urticaria were reported online in the New England Journal of Medicine this week.. Urticaria (hives) occurs when mast cells in the skin are triggered to release histamine and other inflammatory mediators stored in cytoplasmic granules (degranulation). In acute urticaria due to allergic reactions, degranulation is triggered when allergen is bound by IgE antibodies attached to FcεRI receptors on the mast cell surface. However, chronic urticaria is not IgE mediated and the mechanism by which mast cells are triggered to degranulate and release histamine is not known.. Omalizumab is a recombinant humanized monoclonal antibody which binds rapidly to circulating IgE, inhibiting its attachment to FcεRI receptors on basophils and mast cells. Expression of FcεRI receptors in basophils is downregulated within 2 weeks, and within 8 weeks there is reduced ...

Mastocytosis, also known as mast cell disease, is an uncommon disorder caused by the accumulation of a normally rare white blood cell type called mast cells. Normal mast cells are involved in fighting certain infections but are most well known as the primary cells that drive allergic responses. When someone has abnormal accumulations of mast cells in the skin, bone marrow, and

Mast cell chymase antibody [CC1] (chymase 1, mast cell) for ELISA, IHC-Fr, IHC-P, WB. Anti-Mast cell chymase mAb (GTX75583) is tested in Human samples. 100% Ab-Assurance.