Cell Degranulation: The process of losing secretory granules (SECRETORY VESICLES). This occurs, for example, in mast cells, basophils, neutrophils, eosinophils, and platelets when secretory products are released from the granules by EXOCYTOSIS.Mast Cells: Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the BASOPHILS, mast cells contain large amounts of HISTAMINE and HEPARIN. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the STEM CELL FACTOR.p-Methoxy-N-methylphenethylamine: A potent mast cell degranulator. It is involved in histamine release.Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects.Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.Passive Cutaneous Anaphylaxis: An evanescent cutaneous reaction occurring when antibody is injected into a local area on the skin and antigen is subsequently injected intravenously along with a dye. The dye makes the rapidly occurring capillary dilatation and increased vascular permeability readily visible by leakage into the reaction site. PCA is a sensitive reaction for detecting very small quantities of antibodies and is also a method for studying the mechanisms of immediate hypersensitivity.Receptors, IgE: Specific molecular sites on the surface of B- and T-lymphocytes which combine with IgEs. Two subclasses exist: low affinity receptors (Fc epsilon RII) and high affinity receptors (Fc epsilon RI).Immunoglobulin E: An immunoglobulin associated with MAST CELLS. Overexpression has been associated with allergic hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).beta-N-Acetylhexosaminidases: A hexosaminidase specific for non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides. It acts on GLUCOSIDES; GALACTOSIDES; and several OLIGOSACCHARIDES. Two specific mammalian isoenzymes of beta-N-acetylhexoaminidase are referred to as HEXOSAMINIDASE A and HEXOSAMINIDASE B. Deficiency of the type A isoenzyme causes TAY-SACHS DISEASE, while deficiency of both A and B isozymes causes SANDHOFF DISEASE. The enzyme has also been used as a tumor marker to distinguish between malignant and benign disease.Cromolyn Sodium: A chromone complex that acts by inhibiting the release of chemical mediators from sensitized mast cells. It is used in the prophylactic treatment of both allergic and exercise-induced asthma, but does not affect an established asthmatic attack.Cytoplasmic Granules: Condensed areas of cellular material that may be bounded by a membrane.Histamine: An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter.Tryptases: A family of neutral serine proteases with TRYPSIN-like activity. Tryptases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.Ketotifen: A cycloheptathiophene blocker of histamine H1 receptors and release of inflammatory mediators. It has been proposed for the treatment of asthma, rhinitis, skin allergies, and anaphylaxis.Anti-Allergic Agents: Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475)NorbornanesBasophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes.Basophil Degranulation Test: An in vitro test used in the diagnosis of allergies including drug hypersensitivity. The allergen is added to the patient's white blood cells and the subsequent histamine release is measured.Complement C3a: The smaller fragment generated from the cleavage of complement C3 by C3 CONVERTASE. C3a, a 77-amino acid peptide, is a mediator of local inflammatory process. It induces smooth MUSCLE CONTRACTION, and HISTAMINE RELEASE from MAST CELLS and LEUKOCYTES. C3a is considered an anaphylatoxin along with COMPLEMENT C4A; COMPLEMENT C5A; and COMPLEMENT C5A, DES-ARGININE.Edema: Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.Chymases: A family of neutral serine proteases with CHYMOTRYPSIN-like activity. Chymases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.Gliotoxin: A fungal toxin produced by various species of Trichoderma, Gladiocladium fimbriatum, Aspergillus fumigatus, and Penicillium. It is used as an immunosuppressive agent.Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.Histamine Antagonists: Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only.Allergens: Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress.Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin.Capillary Permeability: The property of blood capillary ENDOTHELIUM that allows for the selective exchange of substances between the blood and surrounding tissues and through membranous barriers such as the BLOOD-AIR BARRIER; BLOOD-AQUEOUS BARRIER; BLOOD-BRAIN BARRIER; BLOOD-NERVE BARRIER; BLOOD-RETINAL BARRIER; and BLOOD-TESTIS BARRIER. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (TIGHT JUNCTIONS) which may limit large molecule movement.Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.Pyrilamine: A histamine H1 antagonist. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies.Streptomycetaceae: A family of soil bacteria. It also includes some parasitic forms.Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins.Receptors, Prostaglandin E, EP1 Subtype: A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GQ and the subsequently activates TYPE C PHOSPHOLIPASES. Additional evidence has shown that the receptor can act through a calcium-dependent signaling pathway.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses.Conjunctivitis, Allergic: Conjunctivitis due to hypersensitivity to various allergens.Receptors, Prostaglandin E, EP3 Subtype: A subtype of prostaglandin E receptors that specifically couples to GTP-BINDING PROTEIN ALPHA SUBUNIT, GI and subsequently inhibits ADENYLYL CYCLASES.Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.Mice, Inbred C57BLCells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Methysergide: An ergot derivative that is a congener of LYSERGIC ACID DIETHYLAMIDE. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the CELL MEMBRANE.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Dermatitis: Any inflammation of the skin.Antigens: Substances that are recognized by the immune system and induce an immune reaction.Reagins: Antibodies, especially IGE, that bind to tissue of the same species so that ANTIGENS induce release of HISTAMINE and other vasoactive agents. HYPERSENSITIVITY is the clinical manifestation.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Mastocytosis: A heterogenous group of disorders characterized by the abnormal increase of MAST CELLS in only the skin (MASTOCYTOSIS, CUTANEOUS), in extracutaneous tissues involving multiple organs (MASTOCYTOSIS, SYSTEMIC), or in solid tumors (MASTOCYTOMA).Eosinophil Peroxidase: A 66-kDa peroxidase found in EOSINOPHIL granules. Eosinophil peroxidase is a cationic protein with a pI of 10.8 and is comprised of a heavy chain subunit and a light chain subunit. It possesses cytotoxic activity towards BACTERIA and other organisms, which is attributed to its peroxidase activity.Mice, Inbred BALB CSignal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Receptors, Neurotensin: Cell surface proteins that bind neurotensin with high affinity and trigger intracellular changes which influence the behavior of cells. Neurotensin and neurotensin receptors are found in the central nervous system and in the periphery.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Receptors, IgG: Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the STOMACH. The two sacs are connected by the foramen of Winslow, or epiploic foramen.Lysosomal-Associated Membrane Protein 1: An abundant lysosomal-associated membrane protein that has been found to shuttle between LYSOSOMES; ENDOSOMES; and the PLASMA MEMBRANE. In PLATELETS and T-LYMPHOCYTES it may play a role in the cellular degranulation process.Rats, Inbred BNN-Formylmethionine Leucyl-Phenylalanine: A formylated tripeptide originally isolated from bacterial filtrates that is positively chemotactic to polymorphonuclear leucocytes, and causes them to release lysosomal enzymes and become metabolically activated.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Neutrophil Infiltration: The diffusion or accumulation of neutrophils in tissues or cells in response to a wide variety of substances released at the sites of inflammatory reactions.Receptor, PAR-2: A G-protein-coupled, proteinase-activated receptor that is expressed in a variety of tissues including ENDOTHELIUM; LEUKOCYTES; and the GASTROINTESTINAL TRACT. The receptor is activated by TRYPSIN, which cleaves off the N-terminal peptide from the receptor. The new N-terminal peptide is a cryptic ligand for the receptor. The uncleaved receptor can also be activated by the N-terminal peptide present on the activated THROMBIN RECEPTOR and by small synthetic peptides that contain the unmasked N-terminal sequence.Splanchnic Circulation: The circulation of blood through the BLOOD VESSELS supplying the abdominal VISCERA.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Receptors, Prostaglandin E, EP2 Subtype: A subtype of prostaglandin E receptors that specifically couples to GS ALPHA GTP-BINDING PROTEIN SUBUNITS and subsequently activates ADENYLYL CYCLASES.Killer Cells, Natural: Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Antigens, CD63: Ubiquitously-expressed tetraspanin proteins that are found in late ENDOSOMES and LYSOSOMES and have been implicated in intracellular transport of proteins.Leukemia, Basophilic, Acute: A rare acute myeloid leukemia in which the primary differentiation is to BASOPHILS. It is characterized by an extreme increase of immature basophilic granulated cells in the bone marrow and blood. Mature basophils are usually sparse.Serine Proteinase Inhibitors: Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES.Cell Count: The number of CELLS of a specific kind, usually measured per unit volume or area of sample.Leukocytes: White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Bronchial Hyperreactivity: Tendency of the smooth muscle of the tracheobronchial tree to contract more intensely in response to a given stimulus than it does in the response seen in normal individuals. This condition is present in virtually all symptomatic patients with asthma. The most prominent manifestation of this smooth muscle contraction is a decrease in airway caliber that can be readily measured in the pulmonary function laboratory.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Neutrophil Activation: The process in which the neutrophil is stimulated by diverse substances, resulting in degranulation and/or generation of reactive oxygen products, and culminating in the destruction of invading pathogens. The stimulatory substances, including opsonized particles, immune complexes, and chemotactic factors, bind to specific cell-surface receptors on the neutrophil.Inflammation Mediators: The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).Lactoferrin: An iron-binding protein that was originally characterized as a milk protein. It is widely distributed in secretory fluids and is found in the neutrophilic granules of LEUKOCYTES. The N-terminal part of lactoferrin possesses a serine protease which functions to inactivate the TYPE III SECRETION SYSTEM used by bacteria to export virulence proteins for host cell invasion.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.Cell Adhesion: Adherence of cells to surfaces or to other cells.Phosphoric Monoester Hydrolases: A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.

Borrelia burgdorferi spirochetes induce mast cell activation and cytokine release. (1/1340)

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

Potent mast cell degranulation and vascular permeability triggered by urocortin through activation of corticotropin-releasing hormone receptors. (2/1340)

Urocortin (Ucn) is related to corticotropin-releasing hormone (CRH), and both are released in the brain under stress where they stimulate CRH 1 and 2 receptors (CRHR). Outside the brain, they may have proinflammatory actions through activation of mast cells, which are located perivascularly close to nerve endings and degranulate in response to acute psychological stress. Here, we report that a concentration of intradermal Ucn as low as 10 nM induced dose-dependent rat skin mast cell degranulation and increased vascular permeability. This effect appeared to be equipotent to that of calcitonin gene-related peptide and neurotensin. Ucn-induced skin vasodilation was inhibited by pretreatment with the mast cell stabilizer disodium cromoglycate (cromolyn) and was absent in the mast cell-deficient W/Wv mice. The selective nonpeptide CRH receptor 1 antagonist, antalarmin and the nonselective peptide antagonist astressin both reduced vascular permeability triggered by Ucn but not that by Substance P or histamine. In contrast, the peptide antagonist alpha-helical CRH-(9-41) reduced the effect of all three. The vasodilatory effect of Ucn was largely inhibited by pretreatment with H1 receptor antagonists, suggesting that histamine is the major mediator involved in vitro. Neuropeptide depletion of sensory neurons, treatment with the ganglionic blocker hexamethonium, or in situ skin infiltration with the local anesthetic lidocaine did not affect Ucn-induced vascular permeability, indicating that its in situ effect was not mediated through the peripheral nervous system. These results indicate that Ucn is one of the most potent triggers of rat mast cell degranulation and skin vascular permeability. This effect of Ucn may explain stress-induced disorders, such as atopic dermatitis or psoriasis, and may lead to new forms of treatment.  (+info)

A functional granulocyte colony-stimulating factor receptor is required for normal chemoattractant-induced neutrophil activation. (3/1340)

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor that is widely used to treat neutropenia. In addition to stimulating polymorphonuclear neutrophil (PMN) production, G-CSF may have significant effects on PMN function. Because G-CSF receptor (G-CSFR)-deficient mice do not have the expected neutrophilia after administration of human interleukin-8 (IL-8), we examined the effect of the loss of G-CSFR on IL-8-stimulated PMN function. Compared with wild-type PMNs, PMNs isolated from G-CSFR-deficient mice demonstrated markedly decreased chemotaxis to IL-8. PMN emigration into the skin of G-CSFR-deficient mice in response to IL-8 was also impaired. Significant chemotaxis defects were also seen in response to N-formyl-methionyl-leucyl-phenylalanine, zymosan-activated serum, or macrophage inflammatory protein-2. The defective chemotactic response to IL-8 does not appear to be due to impaired chemoattractant receptor function, as the number of IL-8 receptors and chemoattractant-induced calcium influx, actin polymerization, and release of gelatinase B were comparable to those of wild-type PMNs. Chemoattractant-induced adhesion of G-CSFR-deficient PMNs was significantly impaired, suggesting a defect in beta2-integrin activation. Collectively, these data demonstrate that selective defects in PMN activation are present in G-CSFR-deficient mice and indicate that G-CSF plays an important role in regulating PMN chemokine responsiveness.  (+info)

Neurotensin is a proinflammatory neuropeptide in colonic inflammation. (4/1340)

The neuropeptide neurotensin mediates several intestinal functions, including chloride secretion, motility, and cellular growth. However, whether this peptide participates in intestinal inflammation is not known. Toxin A, an enterotoxin from Clostridium difficile, mediates pseudomembranous colitis in humans. In animal models, toxin A causes an acute inflammatory response characterized by activation of sensory neurons and intestinal nerves and immune cells of the lamina propria. Here we show that neurotensin and its receptor are elevated in the rat colonic mucosa following toxin A administration. Pretreatment of rats with the neurotensin receptor antagonist SR-48, 692 inhibits toxin A-induced changes in colonic secretion, mucosal permeability, and histologic damage. Exposure of colonic explants to toxin A or neurotensin causes mast cell degranulation, which is inhibited by SR-48,692. Because substance P was previously shown to mediate mast cell activation, we examined whether substance P is involved in neurotensin-induced mast cell degranulation. Our results show that neurotensin-induced mast cell degranulation in colonic explants is inhibited by the substance P (neurokinin-1) receptor antagonist CP-96,345, indicating that colonic mast activation in response to neurotensin involves release of substance P. We conclude that neurotensin plays a key role in the pathogenesis of C. difficile-induced colonic inflammation and mast cell activation.  (+info)

Mucosal mast cell secretion processes imaged using three-photon microscopy of 5-hydroxytryptamine autofluorescence. (5/1340)

The secretion process of the mucosal mast cell line RBL-2H3 was imaged using infrared three photon excitation (3PE) of serotonin (5-hydroxytryptamine, 5-HT) autofluorescence, a measurement previously difficult because of the technical intractability of deep UV optics. Images of prestimulation 5-HT distributions were analyzed in loaded cell populations (those incubated in a 5-HT-rich medium overnight) and in unloaded populations and were found to be strictly quantifiable by comparison with bulk population high-performance liquid chromatography measurements. Antigenically stimulated cells were observed to characteristically ruffle and spread as granular 5-HT disappeared with no detectable granule movement. Individual cells exhibited highly heterogeneous release kinetics, often with quasi-periodic bursts. Neighboring granule disappearances were correlated, indicative of either spatially localized signaling or granule-granule interactions. In one-half of the granule release events, weak residual fluorescence was visible suggestive of leftover 5-HT still bound to the granule matrix. The terminal stages of secretion (>300 s) consisted primarily of unresolved granules and remainder 5-HT leakage from already released granules.  (+info)

Tracking single secretory granules in live chromaffin cells by evanescent-field fluorescence microscopy. (6/1340)

We have observed secretory granules beneath the plasma membrane of chromaffin cells. Using evanescent-field excitation by epiillumination, we have illuminated a thin layer of cytosol where cells adhere to glass coverslips. Up to 600 frames could be recorded at diffraction-limited resolution without appreciable photodynamic damage. We localized single granules with an uncertainty of approximately 30 nm and tracked their motion in three dimensions. Granules in resting cells wander randomly as if imprisoned in a cage that leaves approximately 70 nm space around a granule. The "cage" itself moves only slowly (D = 2 x 10(-12) cm2/s). Rarely do granules arrive at or depart from the plasma membrane of resting cells. Stimulation increases lateral motion only slightly. After the plasma membrane has been depleted of granules by exocytosis, fresh granules can be seen to approach it at an angle. The method will be useful for exploring the molecular steps preceding exocytosis at the level of single granules.  (+info)

LXA4, aspirin-triggered 15-epi-LXA4, and their analogs selectively downregulate PMN azurophilic degranulation. (7/1340)

The eicosanoid lipoxin A4 (LXA4) is biosynthesized in vivo by cells present at inflammatory sites and appears to be an endogenous anti-inflammatory mediator. Further, in the presence of aspirin, the 15-epimer of LXA4 (15-epi-LXA4) is biosynthesized and may mediate some of aspirin's desirable bioactions. LXA4, 15-epi-LXA4, and their stable analogs inhibit inflammation in established animal models, indicating that these compounds may be useful for treating inflammatory disease states. To investigate the cellular mechanisms by which these lipid mediators downregulate inflammation, we investigated whether these eicosanoids could influence receptor-mediated degranulation of human neutrophils, an event thought to play a major causative role in several inflammatory disease states. LXA4, 15-epi-LXA4, and their stable analogs potently (IC50 < 1 nM) and selectively downregulated neutrophil release of azurophilic granule contents but did not affect other neutrophil secretory functions. Thus the cellular basis of action of these natural off-switches to inflammation appears to involve downregulation of neutrophil azurophilic granule release.  (+info)

Nerve growth factor modifies the expression of inflammatory cytokines by mast cells via a prostanoid-dependent mechanism. (8/1340)

Nerve growth factor (NGF) is well recognized to have a number of potent effects on mast cells, including increasing mast cell numbers in vivo and inducing mast cell degranulation in vitro. More recently, NGF has been demonstrated to induce PGD2 production by mast cells through the induction of mast cell cyclooxygenase expression. We have observed that NGF at doses as low as 10 ng/ml will induce IL-6 production and inhibit TNF-alpha release from rat peritoneal mast cells in the presence of lysophosphatidylserine as a cofactor. NGF synergizes with LPS treatment of peritoneal mast cells (PMC) for the induction of IL-6. Examination of the mechanism of this phenomenon has revealed that NGF can induce both rat PMC and mouse bone marrow-derived cultured mast cells to produce substantial levels of PGE2. This response is maximal at later time points 18-24 h after NGF activation. The ability of NGF to induce PGE2 is not dependent on mast cell degranulation. Other stimuli capable of inducing IL-6, such as LPS, do not induce production of this prostanoid. Inhibition of cyclooxygenase activity by PMC using either flurbiprofen or indomethacin inhibited both the NGF-induced PGE2 synthesis and the NGF-induced alterations in TNF-alpha and IL-6 production. These results suggest a role for mast cell-derived prostanoids in the regulation of local inflammatory responses and neuronal degeneration after tissue injury involving induction of NGF production.  (+info)

*Mast cell

... and biomarkers of mast cell degranulation. Unlike other hematopoietic cells of the immune system, mast cells naturally occur in ... Other neoplastic disorders associated with mast cells include mast cell sarcoma and mast cell leukemia. Mast cell activation ... connective tissue-type mast cells and mucosal mast cells. The activities of the latter are dependent on T-cells. Mast cells are ... "Distinguishing mast cell and granulocyte differentiation at the single-cell level". Cell Stem Cell. 6: 361-8. doi:10.1016/j. ...

*MCD peptide

The histamine releasing function of MCD peptide, at low concentrations, causes the degranulation of mast cell , and shows anti- ... For its immunotoxic properties, a low concentration of MCD peptide can cause mast cell degranulation by releasing histamine; at ... The MCD peptide has an immunotoxic effect on mast cells by releasing histamine from these cells. MCD peptide has also been ... Buku, A; Priceb, JA; Mendlowitzc, M; Masurd, S (2001). "Mast cell degranulating peptide binds to RBL-2H3 mast cell receptors ...

*Allergic bronchopulmonary aspergillosis

The reaction of IgE with Aspergillus antigens results in mast cell degranulation with bronchoconstriction and increased ... These cytokines up-regulate mast cell degranulation, exacerbating respiratory decline. Aspergillus also utilises a number of ... "Lack of IL-4 receptor expression on T helper cells reduces T helper 2 cell polyfunctionality and confers resistance in allergic ... Type 2 T helper cells appear to play an important role in ABPA due to an increased sensitivity to interleukin (IL) 4 and IL-5. ...

*YKT6

Puri N, Kruhlak MJ, Whiteheart SW, Roche PA (Nov 2003). "Mast cell degranulation requires N-ethylmaleimide-sensitive factor- ... The Journal of Cell Biology. 157 (1): 45-62. doi:10.1083/jcb.200112127. PMC 2173270 . PMID 11927603. Xu Y, Martin S, James DE, ... The Journal of Cell Biology. 157 (1): 45-62. doi:10.1083/jcb.200112127. PMC 2173270 . PMID 11927603. Xu Y, Martin S, James DE, ... Molecular Biology of the Cell. 13 (10): 3493-507. doi:10.1091/mbc.E02-01-0004. PMC 129961 . PMID 12388752. Maruyama K, Sugano S ...

*NLN (gene)

Neurotensin is involved in many processes including mast cell degranulation and regulation of central nervous system ... "Neurotensin mediates rat bladder mast cell degranulation triggered by acute psychological stress". Urology. 53 (5): 1035-40. ... "A neurotensin receptor antagonist inhibits acute immobilization stress-induced cardiac mast cell degranulation, a corticotropin ... It is a 78-kDa enzyme, widely distributed in mammalian tissues and found in various subcellular locations that vary with cell ...

*Chronic prostatitis/chronic pelvic pain syndrome

"Neurotensin mediates rat bladder mast cell degranulation triggered by acute psychological stress". Urology. 53 (5): 1035-40. ... In the inflammatory form, urine, semen, and other fluids from the prostate contain pus cells (dead white blood cells or WBCs), ... CP/CPPS may be inflammatory (Category Ⅲa) or non-inflammatory (Category Ⅲb), based on levels of pus cells in expressed ... CS1 maint: Multiple names: authors list (link) Theoharides TC, Cochrane DE; Cochrane (2004). "Critical role of mast cells in ...

*INPP5D

"Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation". Molecular and Cellular Biology. 22 ... INPP5D also called SHIP1 was also shown to be a negative regulator of BCR signalling in B cells. This gene is a member of the ... van Dijk TB, van Den Akker E, Amelsvoort MP, Mano H, Löwenberg B, von Lindern M (November 2000). "Stem cell factor induces ... Expression of this protein is restricted to hematopoietic cells where its movement from the cytosol to the plasma membrane is ...

*Anaphylaxis

Non-immunologic mechanisms involve substances that directly cause the degranulation of mast cells and basophils. These include ... cause anaphylaxis by directly triggering mast cell degranulation. The frequency of a reaction to an agent partly depends on the ... The coronary spasm is related to the presence of histamine-releasing cells in the heart. While a fast heart rate caused by low ... reactions are a type of anaphylaxis that does not involve an allergic reaction but is due to direct mast cell degranulation. ...

*Damage-associated molecular pattern

... as occurs in necrotic cell death. Extracellular ATP triggers mast cell degranulation by signaling through P2X7 receptors. ... When released outside the cell or exposed on the surface of the cell following tissue injury, they move from a reducing to an ... Also, following necrosis (a kind of cell death), tumor DNA is released outside the nucleus, and outside the cell, and becomes a ... as well as upregulate expression of cell adhesion molecules (ICAM-1, VCAM-1) on endothelial cells.[citation needed] The ...

*Antibody

... lysis of cells (binding to complement), and degranulation of mast cells, basophils, and eosinophils (binding to FcεR). In ... B cell activation follows engagement of the cell-bound antibody molecule with an antigen, causing the cell to divide and ... In most cases, interaction of the B cell with a T helper cell is necessary to produce full activation of the B cell and, ... The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been ...

*Aquagenic urticaria

This can also help inhibit mast cell degranulation which may contribute to the presence of aquagenic urticaria. PUVA therapy: ... Absorption of this substance would exert an effect of perifollicular mast cell degranulation with release of histamine. ... Beaven, M. A. (2009). "Our perception of the mast cell from Paul Ehrlich to now". European Journal of Immunology. 39 (1): 11-25 ... The discovery of mast cells by Paul Ehrlich in 1879 brought urticaria and similar conditions under a comprehensive idea of ...

*Degranulation

... and mast cells. It is also used by certain lymphocytes such as natural killer (NK) cells and cytotoxic T cells, whose main ... Basophil activation Cell Degranulation at the US National Library of Medicine Medical Subject Headings (MeSH) Yamasaki S, Saito ... Cytotoxic T cells and NK cells release molecules like perforin and granzymes by a process of directed exocytosis to kill ... via the activation of tyrosine kinases within the cell. The mast cell releases a mixture of compounds, including histamine, ...

*Vancomycin

These findings are due to interaction of vancomycin with MRGPRX2, a GPCR mediating IgE-independent mast cell degranulation. ... This binding of vancomycin to the D-Ala-D-Ala prevents cell wall synthesis of the long polymers of N-acetylmuramic acid (NAM) ... It is a type of glycopeptide antibiotic and works by blocking the construction of a cell wall. Vancomycin was first sold in ... Due to the different mechanism by which Gram-negative bacteria produce their cell walls and the various factors related to ...

*Codeine

... intravenous injection is contraindicated as this can result in non-immune mast-cell degranulation and resulting anaphylactoid ...

*Mast cell stabilizer

They block mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators ... Mast cell stabilizers are cromone medications used to prevent or control certain allergic disorders. ... Mast cell stabilizer medications include: β2-adrenergic agonists Cromoglicic acid Ketotifen Methylxanthines[citation needed] ... Without intracellular calcium, the histamine vesicles cannot fuse to the cell membrane and degranulate. As inhalers they are ...

*Complement component 5a

Both C5a and C5a des-Arg can trigger mast cell degranulation, releasing proinflammatory molecules histamine and TNF-α. C5a is ... initiating accumulation of complement and phagocytic cells at sites of infection or recruitment of antigen-presenting cells to ... White blood cells are activated by upregulation of integrin avidity, the lipoxygenase pathway and arachidonic acid metabolism. ... Manthey HD, Woodruff TM, Taylor SM, Monk PN (2009). "Complement component 5a (C5a)". Int J Biochem Cell Biol. 41 (11): 2114-7. ...

*Compound 48/80

It promotes histamine release, and in biochemical research, compound 48/80 is used to promote mast cell degranulation.[citation ...

*Lipid raft

"A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation". International ... T cell antigen receptor (TCR) is a molecule found on the surface of T lymphocytes (T cells). It is composed of αβ-heterodimers ... Gupta, Neetu; Defranco, Anthony L. (2007). "Lipid rafts and B cell signaling". Seminars in Cell & Developmental Biology. 18 (5 ... T cell antigen receptor signalling, B cell antigen receptor signalling, EGF receptor signalling, insulin receptor signalling ...

*Urticaria pigmentosa

Another mast cell stabilizer Gastrocrom, a form of cromoglicic acid has also been used to reduce mast cell degranulation. ... The bug bites are actually the clumps of mast cells. Doctors can confirm the presence of mast cells by rubbing the baby's skin ... c-kit is a transmembrane protein which, when bound to Mast Cell Growth Factor (MCGF), signals the cell to divide. Mutations in ... may reduce mast cell degranulation in patients with urticaria pigmentosa. A 1984 study by Fairly et al. included a patient with ...

*Umbellulone

CGRP binding to its receptor will also promote mast cell degranulation and infiltration by neutrophils and other immune cells. ... Calcium will enter the cell and the cell membrane will be depolarised. Depolarisation of the membrane will result in the ... Red blood cells will be less able to nurture organs with oxygen. Therefore, the probability for a hypoxia increases. ... The increase in immune cells and its inflammatory response is thought to be the main cause of the occurrence of migraine. Its ...

*PRKCD

"Protein kinase C-delta is a negative regulator of antigen-induced mast cell degranulation". Mol. Cell. Biol. 22 (12): 3970-80. ... "Identification of phospholipase C gamma1 as a protein tyrosine phosphatase mu substrate that regulates cell migration". J. Cell ... Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein ... Studies both in human and mice demonstrate that this kinase is involved in B cell signaling and in the regulation of growth, ...

*Kounis syndrome

Also opioids, indicated to relieve chest pain, may induce massive mast cell degranulation which in turn will worsen the ... Mast cell activation and release of inflammatory cytokines from the reaction leads to spasm of the artery leading to the heart ... Antihistamine and mast cell stabilizers e.g. cromoglicate or nedocromil can be also considered. acute coronary event protocol ... markers of mast cell activation are found in people with ACS. Three variants of Kounis syndrome are recognised: Type I occurs ...

*Hypoallergenic dog food

Once binding occurs, mast cell degranulation follows, releasing granules that initiate the symptoms of an allergic reaction in ... Vitamin A is involved in cell growth and division, as well as hair growth and skin maintenance. Since some of the key symptoms ... This is beneficial to have in hypoallergenic dog food diets to help maintain cell integrity in case damage does occur due to a ... They also help to maintain healthy skin and to maintain cell structure. These n-3 fatty acids are usually incorporated into dog ...

*Allergic conjunctivitis

They block a calcium channel essential for mast cell degranulation, stabilizing the cell, thus preventing the release of ... Mast cell intermediaries cause an allergic inflammation and symptoms through the activation of inflammatory cells. When ... Doctors commonly prescribe lodoxamide and nedocromil as mast cell stabilizers, which come as eye drops. A mast cell stabilizer ... epithelial cells, mast cells, and TH2 lymphocytes aggravate the biochemistry and histology of the conjunctiva. VKC is a disease ...

*Mastocytosis

At least one clinical study suggested nifedipine, one of the dihydropyridines, may reduce mast cell degranulation in patients ... Other known but rare mast cell proliferation diseases are mast cell leukemia and mast cell sarcoma. No one is sure how many ... Mast cells express a cell surface receptor, c-kit (CD117), which is the receptor for stem cell factor (scf). In laboratory ... Mast cells collect in various tissues and can affect organs where mast cells do not normally inhabit such as the liver, spleen ...

*N-Arachidonoyl dopamine

Finally, NADA can prevent the degranulation and release of TNF from RBL- 2H3 mast cells treated with an IgE-antigen complex. ... Additionally, NADA has been observed to suppress inflammatory activation of human Jurkat T cells and to inhibit the release of ... "Inhibitory effect of N-Acyl dopamines on IgE-mediated allergic response in RBL-2H3 cells". Lipids. 48 (4): 383-393. doi:10.1007 ... NADA also promotes the inflammatory resolution of human endothelial cells activated by both endogenous (i.e. TNF) and exogenous ...
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
To provide a cellular basis for the increased cutaneous anaphylaxis in Coro1a−/−Coro1b−/− mice, we examined FcεRI-mediated MC degranulation in coronin-deficient BMMCs by measuring the release of β-hexosaminidase from prestored MC granules. Interestingly, antigen-mediated cross-linking of FcεRI resulted in significantly enhanced release of β-hexosaminidase activity from Coro1a−/− BMMCs as compared with WT cells (Fig. 2 b). Although Coro1b−/− BMMCs showed normal degranulation, the additional loss of Coro1b further increased hyperdegranulation in Coro1a−/− BMMCs. For maximal activation, cells were also stimulated with PMA/ionomycin, which overrides the observed hyperdegranulation phenotype of Coro1a−/−Coro1b−/− BMMCs.. Increased FcεRI-mediated degranulation of Coro1a−/− and Coro1a−/−Coro1b−/− BMMCs was further confirmed by assessing the up-regulation of CD107a cell surface expression, which is a marker for granule exocytosis (Fig. 2 c). Again, ...
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 ...
This study demonstrates an important role for the nonreceptor tyrosine kinase Pyk2 in the integrin-mediated activation of PMNs that contributes to normal degranulation responses required for efficient host defense to S. aureus infection. Pyk2-deficient PMNs exhibited reduced degranulation responses following integrin ligation both in vitro and during bacterial infection in vivo; however, they responded normally to soluble agonists, suggesting that the integrin signaling pathway was the major response affected in the pyk2 mutant cells. It is clear that unlike Src-family or Syk tyrosine kinases, Pyk2 is acting in a more distal step in the integrin signaling pathway, because many integrin-mediated functions were normal in pyk2−/− PMNs, including attachment, adhesion, and integrin-mediated activation of superoxide production. These limited impairments correlate with the only partially reduced integrin-mediated tyrosine phosphorylation responses, although reduction in phosphorylation of specific ...
Sigma-Aldrich offers abstracts and full-text articles by [Shenlu Qin, Xumeng Wang, Huanwen Wu, Peng Xiao, Hongqiang Cheng, Xue Zhang, Yuehai Ke].
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Phosphoinositide 3-kinase γ (PI3Kγ) plays a major role in chronic inflammation and allergy. It is a heterodimer of a catalytic p110γ subunit and an adaptor protein, either p101 or the p101 homolog p84 (p87PIKAP). It is unclear whether both PI3Kγ complexes specifically modulate responses such as chemotaxis and degranulation. In mast cells, the p84:p110γ complex synergizes with immunoglobulin E (IgE)- and antigen-clustered FcɛRI receptor signaling and is required to achieve maximal degranulation. During this process, PI3Kγ is activated by ligands of heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs), in particular adenosine receptors, through autocrine and paracrine pathways. Here, we show that p110γ needs p84 to relay signals from GPCRs to formation of phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3], phosphorylation of Akt, migration of cells, and synergistic adenosine-enforced degranulation. Furthermore, the absence of adaptor subunits ...
blood microparticle, extracellular exosome, extracellular matrix, extracellular region, extracellular space, ficolin-1-rich granule lumen, platelet alpha granule lumen, secretory granule lumen, neutrophil degranulation, platelet degranulation
Visit our website to browse Human IgE for mast cell degranulation assays, secondary and control antibodies for ELISA, western blot, IHC or flow cytometry. Save 10% on Human IgE, Secondary and Control Antibody products when you mention the Promo Code received with our monthly emailer at time of order. Offer valid until August 31, 2016. Not valid for distributors and resellers.. Until July 15, 2016 - Buy a Lipodin Kit and Save 20% on Antibodies and Proteins. Abbiotec offers Lipodin-Pro and Lipodin-Ab, protein delivery reagents that transport biologically active proteins and antibodies into living cells. Buy a Lipodin kit and save 20% on catalog proteins and antibodies when you mention the Promo Code received with our monthly emailer at time of order. Offer valid until July 15, 2016. Not valid for distributors and resellers.. ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
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
Mediators pre-stored in neutrophil azurophilic granules are central to the acute inflammatory response and tissue degradation and damage through their proteolytic activity. Different granule populations mobilize and release their content via distinct and hierarchical molecular mechanisms. The molecular mechanisms by which mediators pre-stored in azurophilic granules are mobilized and released to the extracellular space remain largely unknown. We used a number of complementary techniques including; confocal laser scanning microscopy, subcellular fractionation, flow cytometric analyses, Western blot analyses and electron microscopy to examine the ultrastructural and molecular nature of mediator release in neutrophil azurophilic granules. We found that following IL-8 activation, neutrophil azurophilic granules undergo piecemeal degranulation (selective mediator release) leading to altered granule content. Piecemeal degranulation of azurophilic granules is characterized by budding of small secretory ...
Hydroxyl radical (.OH) formation by neutrophils in vitro requires exogenous iron. Two recent studies [Britigan, Rosen, Thompson, Chai & Cohen (1986) J. Biol. Chem. 261, 17026-17032; Winterbourn (1987) J. Clin. Invest. 78, 545-550] both reported that neutrophil degranulation could potentially inhibit the formation of .OH, but differed in their conclusions as to the responsible factor, myeloperoxidase (MPO) or lactoferrin (LF). By using a previously developed spin-trapping system which allows specific on-line detection of superoxide anion (O2-) and .OH production, the impact of MPO and LF release on neutrophil .OH production was compared. When iron-diethylenetriaminepenta-acetic acid-supplemented neutrophils were stimulated with phorbol myristate acetate or opsonized zymosan, .OH formation occurred, but terminated prematurely in spite of continued O2- generation. Inhibition of MPO by azide increased the magnitude, but not the duration, of .OH formation. No azide effect was noted when MPO-deficient ...
Background: The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. Methods and results: Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; ...
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 ...
Other immune cells also play an important role in allergy and the allergic reaction. Activated B cells (or plasma cells) produce the IgE antibodies selectively in allergic individuals. B cells are also able to make other antibodies (including IgG) against allergens that do not lead to mast cell degranulation but are protective against allergic inflammation. Allergen-specific IgG antibody, but not IgE, has been found in nonallergic individuals, demonstrating that their immune systems can also recognize and respond to the allergen, but without inducing an inflammatory response.. When a previously sensitized person comes in contact with the same allergen for the second time, the allergen crosslinks two or more molecules of IgE on the same mast cell or basophil, leading to degranulation. The release of granules causes the effects of inflammation, either systemically or locally at the site of exposure (lungs, skin, etc.). These can include redness, swelling, itchiness, increased vascular ...
Dr. Dean Metcalfe, Head of the Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda MD, USA Coffee is served 15:00. Welcome! About Dean Metcalfe Dr. Metcalfe is a world leading scientist, particularly in the field of mast cell biology and mast cell functions related to human disease. He has published more than 500 scientific papers, including several seminal publications.
Cardiac mast cells store and release a variety of biologically active mediators, several of which have been implicated in the activation of matrix metalloproteinases in the volume-overloaded heart, while others are involved in the fibrotic process in
TY - JOUR. T1 - Acrolein induction of oxidative stress and degranulation in mast cells. AU - Hochman, Daniel J.. AU - Collaco, Christopher R.. AU - Brooks, Edward G. PY - 2014. Y1 - 2014. N2 - Increases in asthma worldwide have been associated epidemiologically with expanding urban air pollution. The mechanistic relationship between airway hyper-responsiveness, inflammation, and ambient airborne triggers remains ambiguous. Acrolein, a ubiquitous aldehyde pollutant, is a product of incomplete combustion reactions. Acrolein is abundant in cigarette smoke, effluent from industrial smokestacks, diesel exhaust, and even hot oil cooking vapors. Acrolein is a potent airway irritant and can induce airway hyper-responsiveness and inflammation in the lungs of animal models. In the present study, we utilized the mast cell analog, RBL-2H3, to interrogate the responses of cells relevant to airway inflammation and allergic responses as a model for the induction of asthma-like conditions upon exposure to ...
IgE binds to the surface of a class of white blood cells called mast cells. The presence of antigen that binds to the IgE leads to the release of granules by the mast cells that contain a number of mediators of inflammation, including histamine. These factors are important in immune response that protect us from parasites, including helminths (worms). Some humans are more likely to make an IgE response to non-pathogenic antigens, including pollens. These individuals suffer from allergies caused by IgE-stimulated mast cell degranulation ...
Degranulation assay of derived MCs.A. A representative result of flow cytometry on original CD34+ hematopoietic precursors using anti-FcεRI and anti-CD117 anti
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 ...
Mast cells are localized in tissues. Intense research on these cells over the years has demonstrated their role as effector cells in the maintenance of tissue integrity following injury produced by infectious agents, toxins, metabolic states etc. After stimulation they release a sophisticated array of inflammatory mediators, cytokines and growth factors to orchestrate an inflammatory response. These mediators can directly initiate tissue responses on resident cells, but they have also been shown to regulate other infiltrating immune cell functions. Research in recent years has revealed that the outcome of mast cell actions is not always detrimental for the host but can also limit disease development. In addition, mast cell functions highly depend on the physiological context in the organism. Depending on the genetic background, strength of the injurious event, the particular microenvironment, mast cells direct responses ranging from pro- to anti-inflammatory. It appears that they have evolved as
Click on a genes description to view its network relationships with genes known to be involved in "regulation of leukocyte degranulation" ...
Alpha-1 antitrypsin (AAT) deficiency (AATD) is characterised by excessive neutrophil degranulation and a protease: anti-protease imbalance leading to premature emphysema. Current specialised treatment for AATD consists of once weekly infusion of plasma purified AAT. Neutrophil degranulation is under the control of small GTP-binding proteins, including Ras-related C3 botulinum toxin substrate 2 (Rac2). The molecular basis for aberrant neutrophil degranulation in AATD has not been elucidated to date. The aim of this study was to fully characterise neutrophil degranulation in AATD and to determine the effects of AAT augmentation therapy on the AATD neutrophil. In this study, we examined degranulation by AATD neutrophils by Western blotting. This revealed a 3-fold increase in levels of myeloperoxidase (MPO), human cathelicidin antimicrobial protein (hCAP-18) and matrix metalloprotease-9 (MMP-9), markers of primary, secondary and tertiary granules, respectively (p=0.023, p=0.036 and p=0.042, respectively).
Looking for basophil degranulation test? Find out information about basophil degranulation test. A white blood cell with granules that stain with basic dyes and are water-soluble Explanation of basophil degranulation test
Effective management of fibromyalgia symptoms is complex and requires a multidisciplinary approach evaluating pain, function and the psychosocial milieu of the fibromyalgia patient. Response and tolerance to treatment varies among patients. Nonpharmacological interventions are a necessity and complement drug therapy. A strategic polypharmacy approach using drugs with different mechanisms of action can be helpful. An organized approach that manages the worst symptom first can facilitate easier management of the other symptoms. Effective symptom control is expanding as the underlying pathophysiology of fibromyalgia becomes clearer. The emergence of novel agents that are more effective in shutting down central sensitization may be more effective in treating this disabling condition. The provider can help by believing in the patient, and evaluating and treating the patient systematically. ...
The therapeutic effect of mitochondria-targeted antioxidant 10-(6´-plastoquinonyl)decyltriphenylphosphonium bromide (SkQ1) in experimental models of acute inflammation and wound repair has been shown earlier. It was suggested that the antiinflammatory activity of SkQ1 is related to its ability to suppress inflammatory activation of the vascular endothelium and neutrophil migration into tissues. Here, we demonstrated that SkQ1 inhibits activation of mast cell (MCs) followed by their degranulation and histamine release in vivo and in vitro. Intraperitoneal injections of SkQ1 in the mouse air-pouch model reduced the number of leukocytes in the air-pouch cavity and significantly decreased the histamine content in it, as well as suppressing MC degranulation in the air-pouch tissue. The direct effect of SkQ1 on MCs was studied in vitro in the rat basophilic leukemia RBL-2H3 cell line. SkQ1 inhibited induced degranulation of RBL-2H3 cells. These results suggest that mitochondrial reactive oxygen ...
Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including granulocytes (neutrophils, basophils, and eosinophils) and mast cells. It is also used by certain lymphocytes such as natural killer (NK) cells and cytotoxic T cells, whose main purpose is to destroy invading microorganisms. Antigens interact with IgE molecules already bound to high affinity Fc receptors on the surface of mast cells to induce degranulation, via the activation of tyrosine kinases within the cell. The mast cell releases a mixture of compounds, including histamine, proteoglycans, serotonin, and serine proteases from its cytoplasmic granules. In a similar mechanism, activated eosinophils release preformed mediators such as major basic protein, and enzymes such as peroxidase, following interaction between their Fc receptors and IgE molecules that 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?. ...
Control of Fyn kinase activity and mast cell degranulation is restored by retroviral transduction of Lyn kinase in Lyn-deficient mast cells. (a) Lyn−/− mast
It took years of immune and DNA testing to finally sort out all the issues. We still have one last mystery to solve having to do with the last stage of NK cell function. Cincinatti Childrens Hospital has some new tests that are fascinating and helping doctors understand better why some people cant finish off a virus or knock out cancer. When you cant respond properly with the high-powered immune attack, its like fighting a war without air strikes. So your only option is to send in loads of ground troops and thats basically what mast cell responses are doing. Theyre trying to protect your weak spots but in doing so, they also cause some collateral damage. If I try to suppress my TH2 responses too much with antihistamines or other mast cell degranulation suppressors, then I get relapses of viruses like EBV ...
Sigma-Aldrich offers abstracts and full-text articles by [Prashanta Silwal, Keuna Shin, Seulgi Choi, Seong Wook Kang, Jin Bong Park, Hyang-Joo Lee, Suk-Jin Koo, Kun-Hoe Chung, Uk Namgung, Kyu Lim, Jun-Young Heo, Jong Il Park, Seung-Kiel Park].
In very severe cases of degranulation, the chemical soup generated by degranulating mast cells may lead to flushing of the body and the face, swelling of the eyes, nose and throat (angioedema), choking responses in the throat and loss of consciousness (anaphylaxis).. Moreover, because erupting (degranulating) mast cells dump high levels of histamines, prostaglandins, heparin, neutral proteases, acid hydrolases, chemokines, cytokines, etc. into the interstitial areas between cells, the body also experiences a form of toxic shock (Hermine et al., 2008). In some cases, the toxic shock is fatal. As if the ones listed arent bad enough, in that "etc." after cytokines there can be dozens of other mediators flooding our bodies all at once!! This is another reason why its soooo important to avoid triggers (and subsequent degranulation) as much as possible. Its not just because it can ruin our day or our week or even because it can cause long term damage to our organs and systems - it can be ...
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 ...
They are produced by the marrow, circulate for five to eight days, and then enter the tissues where they are mysteriously transformed into histiocytes. There are several red blood cell inclusions that are stained by the new methyleneblue stain in addition to the RNA of the reticulocytes. The MCHC cannot exceed the normal value since the erythrocyte cannot be supersaturated with hemoglobin. Meta Cells Cbc Your RBCs are normally all the same color, size, and shape. You can access it through the book outline at this link. Again, these terms will have importance in anemia classification. Further reading on red cell disease Anemia: Pathophysiologic Consequences, Classification, and Clinical Investigation is an introduction to anemia Nutritional Anemias The eos may serve a critical function in mitigating allergic responses, since they can 1) inactivate slow reacting substance of anaphylaxis (SRS-A), 2) neutralize histamine, and 3) inhibit mast cell degranulation. ...
Told ya I wasnt making it up! When I was high histamine it was literally impossible to sleep. I would be up for days at a time. Very handy when I was a journalist working in war zones, but not so great when I have a 9am meeting to go through someones digital strategy. Generally when people tell me theyre very low histamine I ask how their sleep is. Its a great indicator of how youre doing diet-wise. Im not discounting stress, but we know that also causes mast cell degranulation too! Now while the studies I read on valerian took great pains to stress that its not a hypnotic which knocks you into sleep, its an anxiolytic that reduces stress, helping you drop off. Ever wondered why antihistamines make you sleepy? There are a number of reasons - among them is that histamine controls your cicadian rythm/wakefulness hormones, so taking an anti-histamine would naturally make you fall asleep. Given that we know antihistamines make us fat and can cause toxicity syndrome, exploring natural ...
Anaphylaxis is a clinical syndrome often presenting as a medical emergency requiring immediate recognition of symptoms, proper treatment and, if possible, the identification and elimination of risk factors. The symptoms of anaphylaxis are mainly determined by chemicals mediators released upon activation of the immune cells. Mast cells which are abundant in cardiovascular tissues, are the main cells activated during anaphylaxis. Human cardiac mast cells have been identified at the site of sarcolemma, within perivascular tissues, in the adventitia of large coronary arteries, and within coronary plaques. Cardiac mast cells display unique immunological and functional features that make them distinct from mast cells in other tissues. Mast cells play a complex role in the development of several pathological processes in the heart. High affinity receptors for IgE (FcṘI) and for C5a anaphylatoxin are involved in development of systemic and cardiac anaphylactic reactions. Furthermore, in myocardial ...
Mast cells are powerful immune modulators of the tissue microenvironment. Within seconds of activation, these cells release a variety of preformed biologically active products, followed by a wave of mediator synthesis and secretion. Increasing evidence suggests that an intricate network of inhibitory and activating receptors, specific signaling pathways, and adaptor proteins governs mast cell responsiveness to stimuli. Here, we discuss the biological and clinical relevance of negative and positive signaling modalities that control mast cell activation, with an emphasis on novel Fc epsilon RI regulators, immunoglobulin E (IgE)-independent pathways [e.g., Mas-related G protein-coupled receptor X2 (MRGPRX2)], tetraspanins, and the CD300 family of inhibitory and activating receptors.. ...
We are also evaluating whether the augmented vascular permeability, which has been identified in several types of inflammation, including settings that are characterized by piecemeal degranulation of mast cells or basophils, reflects enhanced formation and/or function of endothelial cell vesiculo-vacuolar organelles (VVOs), rather than transport through classical interendothelial cell gaps such as those that develop in postcapillary venules immediately after the administration of large amounts of histamine
Mast cell activation disorders involve an unusual accumulation of mast cells that release histamine and other mediators for inappropriate or unknown reasons and cause inflammation, reports the...
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
Principal Investigator:Taketomi Yoshitaka, Project Period (FY):2016-04-01 - 2018-03-31, Research Category:Grant-in-Aid for Challenging Exploratory Research, Research Field:Biological pharmacy
Mast cells are ubiquitous mediators of inflammation and have been studied for a number of years for their role in asthma, allergies, and anaphylaxis. However, i...
Mast cells are one of the most ancient of immune cells. Theyre foundational to the innate immune system, which is the first line of defense to any invading pathogen. However, they also help to orchestrate some of the behaviors of the newer adaptive immune system. Whats more, they are the sentinels of the body, stationed…
Good info here... my question, as always, is Why? What is the cause? When will the CDC acknowledge the epidemics our country is stricken by? Perhaps because identifying and eliminating the cause would hit the bottom line of too many industries.
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This intraluminal leukocyte is degranulating in a vessel wall injured by dense deposits of presumed immune complexes, EM, 6,000X.. ...
We have worked hard over the 2 years together with our mast manufacturer to develop masts that would have a combination of superior strength and maximum performance. It was agreed to achieve this we would have to slightly change our bends to a slightly stiffer bottom and more flexible top section.
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 ...
Bullous pemphigoid (BP) is an inflammatory subepidermal blistering disease associated with an IgG autoimmune response to the hemidesmosomal protein BP180. Passive transfer of antibodies to the murine BP180 (mBP180) ectodomain triggers a blistering skin disease in mice that depends on complement activation and neutrophil infiltration and closely mimics human BP. In the present study, we show that mast cells (MCs) play a crucial role in experimental BP. Wild-type mice injected intradermally with pathogenic anti-mBP180 IgG exhibited extensive MC degranulation in skin, which preceded neutrophil infiltration and subsequent subepidermal blistering. In contrast, mice genetically deficient in MCs or MC-sufficient mice pretreated with an inhibitor of MC degranulation failed to develop BP. Further, MC-deficient mice reconstituted in skin with MCs became susceptible to experimental BP. Despite the activation of complement to yield C3a and C5a, in the absence of MCs, accumulation of neutrophils at the ...
It all comes down to histamine. Over the last couple of years, medication and diet have established that histamine is a major migraine trigger for me. Clinical evidence as far back as the early 80s supports this notion, with research showing migraineurs have increased levels of histamine in their blood and in studying the role of antihistamines in migraine prevention. More recently, the role of mast cell degranulation (which releases histamine, among other things) in triggering migraines has come to light and is a topic of increasing research interest. (You can learn more about all this in Mast Cell Degranulation Activates a Pain Pathway Underlying Migraine Headache or, the more accessible Hunting for Cells That Trigger Migraine from the National Headache Foundations newsletter.). How is this connected to eating? Certain foods contain histamine and others are considered histamine liberators. Furthermore, histamine is released as part of the digestion process whenever anyone eats anything. And ...
Like some headache patients, many masto sufferers have spent years trying to get a diagnosis for their condition. The symptoms are varied and differ in intensity from one person to another. Some just have the cutaneous version (hives, red spots, Urticaria Pigmentosa, and /or Telangiectasia Macularis Eruptiva Perstans), some have the systemic version which can include all the cutaneous problems and also involves more than one body system (skin, liver, intestines, etc.). Children seldom have the systemic version; it is more common among adults with this syndrome. The systemic version can evolve into more agressive and possibly cancerous versions that involve blood cell production. "Brain fog" and fatigue are often symptoms but are difficult to diagnose ...
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 ...
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 ...
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 ...
Peachell P.T.; Macglashan D.W.Jr; Lichtenstein L.M.; Schleimer R.P., 1988: Regulation of human basophil and lung mast cell function by cyclic amp
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 ...
Allergic asthma is characterized by airway hyperresponsiveness to specific and non-specific stimuli with elevated serum IgE levels and eosinophilic inflammation. It is well known that allergen-specific CD4 + type 2, T-helper (Th2) cells and immunoglobulin E (IgE)-sensitized mast cells are key players in the allergic response. Therefore, therapeutic strategies that induce regulatory T cells (Tregs) to suppress Th2-cell responses and inhibit IgE-mediated activation on mast cells seem to have the greatest potential to efficiently inhibit allergen-induced disorders. Short-chain fatty acids (SCFAs) have anti-inflammatory and immuno-suppressive properties and are considered especially good candidates for the role. Actually, our preliminary results showed that SCFA-phenylbutyrate (PB) induced tolerogenic dendritic cells, enhanced the generation of splenic Foxp3 + Tregs and inhibited mast cell degranulation. PB also expressed a preventive effect in an ovalbumin-induced asthmatic animal model. Therefore, ...
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. ...
The histology of skin lesions is just like nonnecrotizing immune complicated vasculitis-perivascular neutrophilic infiltrates linked with mast cells with minimal endothelial harm.29 British authors have advised that these findings are steady with immune complexes currently being deposited in vessel walls which are quickly removed by neutrophils, followed by mast cell degranulation, neutrophil lysis and macrophage clearance of neutrophil granules.29 The University of Washington Expertise Prior to now 13 years, 17 patients at the University ofWashington are diagnosed as having adult Stills condition. This series of individuals continues to be reported lately in the review posting.lo 6 were from an ongoing series of individuals with fever of undetermined origin. Another 11 instances came from information that have been kindly provided by quite a few individuals. * The situation definition was that ofMedsger and Christy9: large spiking fever without the need of regarded result in; arthralgias or ...
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 ...
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. ...
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 ...
CHAPTER 1 Aggregation of receptors for IgE (Fc RI) causes mast cells and basophils to release preformed contents of granules, including histamine and a variety of enzymes. This process, called degranulation plays a central role in allergic reactions. Methods to study this process are to create multivalent ligands which can interact with the receptors and, in turn, lead to aggregation of the receptors. We prepared a series of fluorophore-labeled divalent and trivalent antigens to study the degranulation of mast cells. Trivalent antigens proved to be much better stimulators for degranulation of mast cells than divalent antigens. These results indicate that aggregates formed by trivalent antigens are more complicated than those of divalent antigens. CHAPTER 2 Membrane-active antibiotics include antimicrobial peptides (AMPs) and a class of amphiphilic steroids termed ceragenins. Recent studies of membrane-active antibiotics show that cationic, facially amphiphilic molecules could disrupt bacterial membranes
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 ...
In this study, we investigated the interactions of Staphylococcus aureus with mast cells, which are multifunctional sentinels lining the surfaces of the body. We found that bone marrow-derived murine mast cells (BMMC) exerted a powerful phagocytosis-independent antimicrobial activity against S. aureus. Both the release of extracellular traps as well as discharge of antimicrobial compounds were the mechanisms used by the BMMC to kill extracellular S. aureus. This was accompanied by the secretion of mediators such as TNF-α involved in the recruitment of effector cells. Interestingly, S. aureus subverted the extracellular antimicrobial activity of the BMMC by internalizing within these cells. S. aureus was also capable to internalize within human mast cells (HMC-1) and within murine skin mast cells during in vivo infection. Bacteria internalization was, at least in part, mediated by the α5β1 integrins expressed on the surface of the mast cell. In the intracellular milieu, the bacterium survived ...
In this study, we investigated the interactions of Staphylococcus aureus with mast cells, which are multifunctional sentinels lining the surfaces of the body. We found that bone marrow-derived murine mast cells (BMMC) exerted a powerful phagocytosis-independent antimicrobial activity against S. aureus. Both the release of extracellular traps as well as discharge of antimicrobial compounds were the mechanisms used by the BMMC to kill extracellular S. aureus. This was accompanied by the secretion of mediators such as TNF-α involved in the recruitment of effector cells. Interestingly, S. aureus subverted the extracellular antimicrobial activity of the BMMC by internalizing within these cells. S. aureus was also capable to internalize within human mast cells (HMC-1) and within murine skin mast cells during in vivo infection. Bacteria internalization was, at least in part, mediated by the α5β1 integrins expressed on the surface of the mast cell. In the intracellular milieu, the bacterium survived ...
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
I think lactic acid plays a big part in our disease. Some people have said mast cells are the culprit for our disease. I think lactic acid helps mast...
mast cells - more links http://geneticgenie.org/blog/2013/01/31/mast-cell-activation-disorder-mcad-chronic-illness-and-its-role-in-methylation/ Ally
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 ...
Eosinophils are potent inflammatory cells with numerous immune functions including antigen presentation and exacerbation of inflammatory responses through their capacity to release a range of largely preformed cytokines and lipid mediators. as well as degranulation evidenced by increased CD63 surface expression secretion of eosinophil cationic protein (ECP) and eosinophil derived neurotoxin (EDN). Moreover NK cells significantly and dose dependently increased eosinophil apoptosis as shown by 4-Chlorophenylguanidine hydrochloride annexin V and propidium iodide (PI) staining. Direct contact was necessary for eosinophil degranulation and apoptosis. 4-Chlorophenylguanidine hydrochloride Increased expression of phosphorylated extracellular signal-regulated kinase (ERK) C13orf1 in cocultured eosinophils and inhibition of eosinophil CD63 expression by pharmacologic inhibitors suggest that MAPK and PI3K pathways are involved in NK cell-induced eosinophil degranulation. Finally we showed that NK cells ...
Mast cells are classically thought to play an important role in protection against helminth infections and in the induction of allergic diseases; however, recent studies indicate that these cells also contribute to neovascularization, which is critical for tissue remodeling, chronic inflammation, and carcinogenesis. Here, we demonstrate that mast cells are essential for sprouting angiogenesis in a murine model of oxygen-induced retinopathy (OIR). Although mouse strains lacking mast cells did not exhibit retinal neovascularization following hypoxia, these mice developed OIR following infusion of mast cells or after injection of mast cell tryptase (MCT). Relative hypoxia stimulated mast cell degranulation via transient receptor potential ankyrin 1. Subsequent surges in MCT stimulated retinal endothelial cells to produce monocyte chemotactic protein-1 (MCP1) and angiogenic factors, leading to sprouting angiogenesis. Mast cell stabilizers as well as specific tryptase and MCP1 inhibitors prevented ...
Type 1 (Immediate Onset) IgE-Mediated Food Allergy IgE-mediated food reactions are immediate in onset and usually involve symptoms such as abdominal cramping, diarrhoea, skin rashes, hives, swelling, wheezing or the most extreme reaction, anaphylaxis. When provoked by a recognised food antigen, IgE antibodies promote mast cell degranulation and the release of histamine and other inflammatory mediators.. Type 3 (Delayed Onset) IgG-Mediated Food Sensitivity IgG-mediated food reactions (also referred to as food sensitivity, food intolerance) are more subtle in their presentation, often occurring hours to days after exposure to food antigens. Unlike IgE-mediated food reactions, IgG-mediated food reactions produce symptoms which are cumulative in nature. Instead of attaching to mast cells, like the IgE antibodies, IgG antibodies bind directly to food as it enters the bloodstream forming circulating immune complexes.. Delayed food reactions may affect any organ or tissue in the body. Common conditions ...
Anaphylactic reaction rarely manifests such as acute coronary syndrome induced by coronary vasospasm or atheromatous plaque rupture due to some chemical mediators, such as histamine, platelet activating factors, cytokines and others, derived from mast cells degranulation.
The calcium channel blockers are a group of drugs which impede calcium ion entry into cells, thereby inhibiting myocardial and smooth muscle contraction, as well as various secretory processes. In theory, these agents might be active in obstructive airways diseases, especially asthma, by blocking airway smooth muscle constriction, mast cell degranulation, mucous gland secretion, and/or vagal neurotransmission. This report reviews the experimental evidence from animal and human studies, both in vitro and in vivo, that the calcium channel blockers inhibit bronchoconstriction. The usefulness of these drugs in patients with the obstructive airways syndromes remains to be determined by future clinical studies ...
Despite many efforts, HIV-1 infection remains a global health problem; an effective vaccine would provide the best chance of controlling the pandemic. Recently, HIV vaccine research has been focusing on the gut mucosal immune system and early immunological events, which may set the stage for the later appearance of clinical immunodeficiency. This thesis describes a method to obtain mucosal tissue, isolate mucosal mononuclear cells (MMC) and study degranulation and intracellular cytokine memory responses using polychromatic flow cytometry. Consistent and reproducible data were generated by adhering to validated Standard Operating Protocols (SOPs). Qualification of such methods is essential for use in vaccine clinical trials. Differences between the magnitude of single CD8 cytokine and degranulation responses between blood and gut were seen; however, the quality of T cell responses at the single cell level was remarkably similar in both compartments. Differences between small bowel and colon were ...
The adenosine A3 receptor, also known as ADORA3, is an adenosine receptor, but also denotes the human gene encoding it. Adenosine A3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. It mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death[citation needed]. Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18). Multiple transcript variants encoding different isoforms have been found for this gene. An adenosine A3 receptor agonist (CF-101) is in clinical trials for the treatment of rheumatoid arthritis. In a mouse model of infarction the A3 ...
Crystallographic and solution studies have shown that IgE molecules are acutely bent in their Fc region. cross-linking by allergen leads to cell degranulation, release of inflammatory mediators and an immediate allergic response. Disruption of the IgE-FcRI conversation is usually a validated strategy for therapeutic intervention in allergic diseases including asthma: an anti-IgE monoclonal IgG antibody, omalizumab (Xolair?, Novartis Pharmaceuticals Ltd), inhibits IgE binding to FcRI and is effective in the Tarafenacin treatment of severe persistent asthma and other allergic diseases2. IgE consists of a dimer of two identical heavy and two identical light chains, but unlike IgG in which the antigen-binding Fab region is separated from the receptor-binding Fc region by a flexible hinge, IgE contains an additional disulphide-linked pair of domains, (C2)2, forming a (C2-C3-C4)2 dimer1. Fluorescence depolarisation studies to assess segmental flexibility have shown IgE to be less flexible than IgG3-6, ...
Background: Heparanase degradation of heparan sulfate plays important roles in a number of pathological processes, including inflammation. In vitro experiments show that heparanase is capable of degrading heparin, a polysaccharide present in mast cells (MCs), in which it has a key role in promoting the storage of secretory granule compounds.. Objective: We sought to investigate the functions of heparanase in MCs.. Methods: Primarily cultured fetal skin-derived mast cells (FSMCs) isolated from embryos and adult peritoneal MCs were analyzed for storage and release of granule molecules in response to MC activation.. Results: FSMCs from heparanase-overexpressing mice contained substantially shorter heparin chains and significantly less proteases than control cells. Conversely, FSMCs lacking heparanase contained heparin of larger size and more proteases than control cells. Correspondingly, heparanase-overexpressing adult MCs exhibited reduced release of heparin-bound proteases, a finding that could ...
Yung, Y and Moore, M A., "Long-term in vitro culture of murine mast cells. Iii. Discrimination of mast cell growth factor and granulocyte-csf." (1982). Subject Strain Bibliography 1982. 4470 ...
The small GTPases of the Ras and Rho families are activated by the key growth factors for mast cell development and survival, SLF and IL-3. While there are many clues that activation of Ras and Rho proteins play critical roles in growth, survival and differentiation, as well as in functions, such as migration and degranulation, limitations in the specificity of experimental tools still obscure their precise functions. There is increasing evidence that differences in subcellular localization of closely related GTPases determines important differences in their function. However, other data also point to differences in sensitivity to activation by GEF and in the effectors they engage ...
Dr. Tilo Brunnee (tilo at brunnee.IN-Berlin.DE) wrote: : Hallo! : I attempt to isolate human mast cell heparin proteoglycan from human lungs. : So far I enzymatically and mechanically prepare a single cell suspension : from human lung, add 4 M Guanidine HCl and sonicate to disrupt the cells : and dialyze against 1M NaCl/10mM Phosphate, pH 6.0 and apply this soup on a : Dowex 1x2-200 ion exchange column equilibrated with the same buffer, elute : with 3M NaCl/10mM Phosphate, dialyze against H2O and speedvac to dryness. : I do have some questions regarding heparin: : - Are there more efficient/more gentle ways to prepare highly sulfated : proteoglycans? : - Are ther any contaminants (that bind to strong ion exchange at pH 6 in : the presence of 1 M NaCl?) to expect from crude human lung? : - Is it true that heparin side chains are bound to a protein core in human : mast cells? : - If so, is the heprain sidechain cleaved from the protein core during or : before degranulation? : - Is there any ...
Method: prospective, monocentric, descriptive study. Primary objective:. Evaluation of the expression and function of receptors activator of NK cell (KIRs) in patients with CLL at stage A with therapeutic abstention, or stage B or C which require a treatment.. Secondary objectives:. Measure of the evolution of cytotoxic function of NK cells and theirs biomarkers of activation when the patient receives an immunochemotherapy with Rituximab/ Fludarabine/ Cyclophosphamide (RCF).. Verification, by analysis, of functions and biomarkers of the adaptive and innate immunity ...
If you have MCAS, there are a number of ways to treat the problem. If you want to minimize your symptoms, a low-histamine diet can greatly alleviate the severity of symptoms related to histamine release. You may also want to investigate your sensitivity to salicylate and oxalate as they can trigger the release of histamine secretion.. As mentioned earlier, a digestive imbalance is the key to MCAS. So if you want to treat the problem, you have to make sure you are eating the right foods to treat the imbalance. Here are 5 nutrients that can greatly reset your body and treat MCAS:. 1. Ensure you are taking in your daily recommended dosage of vitamin C in ester form or buffered form. Taking between a daily dosage of 3,000 to 6,000 milligrams can work exceptionally well as a wonderful anti-histamine. It works by reducing mast cells from releasing histamine and causing histamine to break down at a quicker speed.. 2. In order for vitamin C to function at its optimal level, you should also make sure ...
Mast cells are a type of immune system cell that responds to chemical signals when you get injured. Remember, inflammation is not a bad thing when it does what its supposed to do. If you injure your arm for example, mast cells release a payload of inflammatory chemicals in the surrounding tissue. These chemicals attract white blood cells and activate their immune response against foreign invaders like bacteria to keep you from getting infected. Good thing right? Mast cells also activate pain receptors. Now you may not like that but pain lets you know -- without question - "hey, be careful with that". But overactive mast cell activation induces an increase in the density and sensitivity of pain receptors and can play a part in a variety of chronic pain disorders. Not good ...
Illness related to mold exposure is something that I had heard of, but did not take to heart until recently. This fall I started Kundalini Yoga Teacher Training which required a daily home practice. I set up my yoga props in a cozy corner of the carpeted finished basement and practiced there for at least an hour every day. Kundalini… [Continue reading]. ...
Hives, or uticaria, is an allergic reaction to various antigen triggers, causing raised welts called "wheals" on the surface of the skin. The wheals can be red or white in color; and they can be itchy and/or painful. In acute cases, the wheals tend to appear and disappear suddenly in response to antigen exposure, particularly dietary or drug-induced exposures. Chronic uticaria, however, can last up to 6 months or longer, and research suggests that autoimmunity activates ongoing mast-cell degranulation.. Read More ...
K252b is a staurosporine analog and PKC inhibitor that suppresses DNA synthesis. It also inhibits microbial ectoprotein kinases and inhibits IgE cross-linking-dependent degranulation in basophils.
Confocal micrograph of a stimulated mast cell that has just exploded releasing numerous histamine granules. The remains of the cell are seen towards t...
Dr. Jennifer McClure reflects on evidence about mast cells as a key to chronic disease, providing new insights for physicians, researchers, and the public.
Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF) in cytoplasmic Weibel-Palade bodies (WPBs). We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with or without 75 or 120 μM docosahexaenoic acid or eicosapentaenoic acid for 5 days at 37 °C. WPB degranulation was stimulated using phorbol 12-myristate 13-acetate (PMA), and this was assessed by immunocytochemical staining for vWF. Actin reorganization was determined using phalloidin-TRITC staining. We found that PMA stimulated WPB degranulation, and that this was significantly reduced by prior incubation of cells with LC n-3 PUFAs. In these cells, WPBs had rounded rather than rod-shaped morphology and localized to the perinuclear region, suggesting interference with cytoskeletal remodeling that is necessary for complete WPB
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 ...
Mast cells play a central role in the pathogenesis of allergic reaction. Activation of mast cells by antigens is strictly dependent on the influx of extracellular calcium that involves a complex interaction between signalling molecules located within the cells. We have previously reported that tHGA, an active compound originally isolated from a local shrub known as Melicope ptelefolia, prevented IgE-mediated mast cell activation and passive systemic anaphylaxis by suppressing the release of interleukin-4 (IL-4) and tumour necrosis factor (TNF)-α from activated rat basophilic leukaemia (RBL)-2H3 cells. However, the mechanism of action (MOA) as well as the molecular target underlying the mast cell stabilising effect of tHGA has not been previously investigated. In this study, DNP-IgE-sensitised RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA. To dissect the MOA of tHGA in IgE-mediated mast cell activation, the effect of tHGA on the transcription of IL-4 and TNF-α mRNA was ...
Human subcutaneous white adipose tissue (SC WAT) increases the expression of beige adipocyte genes in the winter. Studies in rodents suggest that a number of immune mediators are important in the beiging response. Here we studied the seasonal beiging response in SC WAT from lean humans. We measured the gene expression of various immune cell markers and performed multivariate analysis of the gene expression data to identify genes that predict UCP1. IL4 and, unexpectedly, the mast cell marker CPA3 predicted UCP1 gene expression. We therefore investigated the effects of mast cells on UCP1 induction by adipocytes. TIB64 mast cells responded to cold by releasing histamine and IL4, and this medium stimulated UCP1 expression and lipolysis by 3T3-L1 adipocytes. Pharmacological block of mast cell degranulation potently inhibited histamine release by mast cells and inhibited adipocyte UCP1 mRNA induction by conditioned medium. Consistent with this, the histamine receptor antagonist chlorpheniramine ...
Biological Process: apoptosis; cell activation; cytokine secretion involved in immune response; defense response to Gram-positive bacterium; detection of diacyl bacterial lipopeptide; detection of triacylated bacterial lipoprotein; I-kappaB phosphorylation; immune response; inflammatory response; innate immune response; interleukin-10 production; learning; leukotriene metabolic process; lipopolysaccharide-mediated signaling pathway; microglia development; microglial cell activation; MyD88-dependent toll-like receptor signaling pathway; myelin formation in the central nervous system; negative regulation of cell proliferation; negative regulation of phagocytosis; negative regulation of synaptogenesis; neutrophil degranulation; nitric oxide metabolic process; positive regulation of chemokine production; positive regulation of inflammatory response; positive regulation of interferon-beta production; positive regulation of interleukin-10 production; positive regulation of interleukin-12 production; ...
Abstract: A significant increase in the myeloperoxidase (MPO) activity has been found in plasma of patients with stable angina and with acute coronary syndrome (ACS) in comparison with the control group. MPO concentration was significantly increased in plasma of ACS patients. Reduced MPO activity in the treated ACS patients correlated with a favorable outcome of the disease. Generally, changes in plasma MPO concentration coincided with changes in lactoferrin concentration thus confirming the role of neutrophil degranulation in the increase of plasma concentrations of these proteins. The increase in MPO activity was obviously determined by modification of the MPO protein caused by reactive oxygen species and halogen in the molar ratio of 1 : 25 and 1 : 50. The decrease in plasma MPO activity may be associated with increased plasma concentrations of the physiological inhibitor of its activity, ceruloplasmin, and also with modification of the MPO protein with reactive oxygen species and halogen at ...
Biological Process: B cell proliferation; B cell receptor signaling pathway; bone marrow development; cell cycle phase transition; cell surface receptor signaling pathway; defense response to virus; dephosphorylation; hemopoietic progenitor cell differentiation; immunoglobulin biosynthetic process; negative regulation of cell adhesion involved in substrate-bound cell migration; negative regulation of cytokine and chemokine mediated signaling pathway; negative regulation of protein kinase activity; negative regulation of T cell mediated cytotoxicity; neutrophil degranulation; positive regulation of antigen receptor-mediated signaling pathway; positive regulation of B cell proliferation; positive regulation of hematopoietic stem cell migration; positive regulation of protein kinase activity; positive regulation of stem cell proliferation; positive regulation of T cell proliferation; protein amino acid dephosphorylation; regulation of cell cycle; release of sequestered calcium ion into cytosol; ...
Crystallographic and solution studies have shown that IgE molecules are acutely bent in their Fc region. cross-linking by allergen leads to cell degranulation, release of inflammatory mediators and an immediate allergic response. Disruption of the IgE-FcRI conversation is usually a validated strategy for therapeutic intervention in allergic diseases including asthma: an anti-IgE monoclonal IgG antibody, omalizumab (Xolair?, Novartis Pharmaceuticals Ltd), inhibits IgE binding to FcRI and is effective in the Tarafenacin treatment of severe persistent asthma and other allergic diseases2. IgE consists of a dimer of two identical heavy and two identical light chains, but unlike IgG in which the antigen-binding Fab region is separated from the receptor-binding Fc region by a flexible hinge, IgE contains an additional disulphide-linked pair of domains, (C2)2, forming a (C2-C3-C4)2 dimer1. Fluorescence depolarisation studies to assess segmental flexibility have shown IgE to be less flexible than IgG3-6, ...
Rationale: Deep vein thrombosis (DVT) and its complication pulmonary embolism have high morbidity reducing quality of life and leading to death. Cellular mechanisms of DVT initiation remain poorly understood. Objective: We sought to determine the role of mast cells (MCs) in DVT initiation and validate MCs as a potential target for DVT prevention. Methods and Results: In a mouse model, DVT was induced by partial ligation (stenosis) of the inferior vena cava (IVC). We demonstrated that two strains of mice deficient for MCs were completely protected from DVT. Adoptive transfer of in vitro differentiated MCs restored thrombosis. Mast cells were present in the venous wall, and the number of granule-containing MCs decreased with thrombosis. Pharmacological depletion of MCs granules or prevention of MC degranulation also reduced DVT. Basal plasma levels of von Willebrand factor and recruitment of platelets to the IVC wall after DVT induction were reduced in MC-deficient mice. Stenosis application ...
Familial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells (lymphocytes) called T cells, natural killer cells, B cells, and macrophages (histiocytes). Excessive amounts of immune system proteins called cytokines are also produced. This overactivation of the immune system causes fever and damages the liver and spleen, resulting in enlargement of these organs.. Familial hemophagocytic lymphohistiocytosis also destroys blood-producing cells in the bone marrow, a process called hemophagocytosis. As a result, affected individuals have low numbers of red blood cells (anemia) and a reduction in the number of platelets, which are involved in clotting. A reduction in platelets may cause easy bruising and abnormal bleeding.. The brain may also be affected in familial hemophagocytic lymphohistiocytosis. As a result, affected individuals may experience irritability, delayed closure of the bones of the skull in infants, neck stiffness, ...
The anti-inflammatory effect of Spirulina platensis (S. platensis) on induced cutaneous immediate-type hypersensitivity in dog was evaluated by using five healthy dogs. The experiments were consisted of 3 periods. At the first time, dogs were received nothing before induced cutaneous immediate-type hypersensitivity reaction using histamine and compound 48/80 intradermally. On the second time, dogs were received dry matter of S. platensis, which compose of phycocyanin being a major compound, for 10 days before they were performed the induction. Then dogs were withdrawn for 14 days, and received antihistamine drug (Hydroxyzine HCl) for 10 days before the induction was done. The immediate reaction was subjectively scored by measuring the diameters of the lesions in millimeters. Skin biopsies were performed and tissue sections were stained to determine the inflammatory cell infiltration and mast cell degranulation in each time of induction. Diameter sizes of wheal, numbers of inflammatory cell in ...
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 ...

Omalizumab efficacy in cases of chronic spontaneous urticaria is not explained by the inhibition of sera activity in effector...Omalizumab efficacy in cases of chronic spontaneous urticaria is not explained by the inhibition of sera activity in effector...

... efficacy in cases of chronic spontaneous urticaria is not explained by the inhibition of sera activity in effector cells ... We found that OmAb added in vitro to sera from CSU patients did not modify the ability of the sera to induce cell degranulation ... In this study, we sought to investigate the ability of OmAb to inhibit mast cell and basophil degranulation induced by sera ... conclude that the beneficial activity of OmAb does not correlate with the ability of patient sera to induce cell degranulation. ...
more infohttps://www.cun.es/en/research/scientific-publications/omalizumab-efficacy-chronic-spontaneous-urticaria-inhibition-sera-activity

Chronic Idiopathic Urticaria Treatment - XOLAIR (Omalizumab)Chronic Idiopathic Urticaria Treatment - XOLAIR (Omalizumab)

Limits mast cell degranulation 6. *Downregulates high-affinity IgE receptors (FcεRI) 1 ...
more infohttps://www.xolairhcp.com/chronic-idiopathic-urticaria.html

Investigate Chronic Urticaria Patients Condition Correlating to C3, C4 of Peripheral Blood--《The Chinese Journal of...Investigate Chronic Urticaria Patient's Condition Correlating to C3, C4 of Peripheral Blood--《The Chinese Journal of...

The Cultivation of Mast Cell Line LAD2 and Establishment of Mast Cell Degranulation Model[J];中国皮肤性病学杂志;2014-01. ... Influence of mizolastine combined with chrysanthemum mixture on function of T helper cell subsets in patients with chronic ... Inhibition of histamine release from sensitized mast cells by antibodies specific for parasite-origina-ted IgE-dependent ... mRNA profiles of cytokine receptors in unstimulated peripheral blood mononuclear cells from patients with chronic idiopathic ...
more infohttp://en.cnki.com.cn/Article_en/CJFDTOTAL-ZBFX201301012.htm

Chronic urticaria: Treatment of refractory symptomsChronic urticaria: Treatment of refractory symptoms

... mediated mast cell degranulation [32], attenuation of neutrophil respiratory burst [33], and inhibition of early-phase events ... and other mediators in mast cells and other cell types [45]. These agents also have anti-T lymphocyte activity [46]. ... Histamine release from mast cells may also be reduced [126]. It has also been used in the management of solar urticaria and ... It is believed to act on plasma cells to reduce autoantibody production in autoimmune CU [102]. Evidence of efficacy is limited ...
more infohttps://www.uptodate.com/contents/chronic-urticaria-treatment-of-refractory-symptoms

Chronic urticaria | Allergy DownunderChronic urticaria | Allergy Downunder

... degranulation is triggered when allergen is bound by IgE antibodies attached to FcεRI receptors on the mast cell surface. ... and within 8 weeks there is reduced FcεRI expression and degranulation by tissue mast cells. ... However, chronic urticaria is not IgE mediated and the mechanism by which mast cells are triggered to degranulate and release ... Urticaria (hives) occurs when mast cells in the skin are triggered to release histamine and other inflammatory mediators ...
more infohttp://allergy.net.au/chronic-urticaria/

cell degranulation Protocols and Video...'cell degranulation' Protocols and Video...

... cell degranulation include Preparation and Use of HIV-1 Infected Primary CD4+ T-Cells as Target Cells in Natural Killer Cell ... A Microplate Assay to Assess Chemical Effects on RBL-2H3 Mast Cell Degranulation: Effects of Triclosan without Use of an ... Isolation of Peritoneum-derived Mast Cells and Their Functional Characterization with Ca2+-imaging and Degranulation Assays, ... Isolation of Functional Cardiac Immune Cells, Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an ...
more infohttps://www.jove.com/keyword/cell+degranulation

JCI -
Different activation signals induce distinct mast cell degranulation strategiesJCI - Different activation signals induce distinct mast cell degranulation strategies

Gaudenzio N, Espagnolle N, Mars LT, Liblau R, Valitutti S, Espinosa E. Cell-cell cooperation at the T helper cell/mast cell ... IκB kinase 2 is essential for IgE-induced mast cell de novo cytokine production but not for degranulation. Cell Rep. 2014;8(5): ... Phosphorylation of SNAP-23 by IκB kinase 2 regulates mast cell degranulation. Cell. 2008;134(3):485-495.. View this article via ... Peritoneal cell-derived mast cells: an in vitro model of mature serosal-type mouse mast cells. J Immunol. 2007;178(10):6465- ...
more infohttps://www.jci.org/articles/view/85538

Frontiers | Purinergic Signaling in Mast Cell Degranulation and Asthma | PharmacologyFrontiers | Purinergic Signaling in Mast Cell Degranulation and Asthma | Pharmacology

... plays a significant role in mast cell degranulation. Both adenosine and ATP can induce degranulation and bronchoconstriction on ... plays a significant role in mast cell degranulation. Both adenosine and ATP can induce degranulation and bronchoconstriction on ... This review will summarize the currently available knowledge on the role of purinergic signaling in mast cell degranulation and ... This review will summarize the currently available knowledge on the role of purinergic signaling in mast cell degranulation and ...
more infohttps://www.frontiersin.org/articles/10.3389/fphar.2017.00947/full

Frontiers | Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment | ImmunologyFrontiers | Mast Cell Degranulation Exacerbates Skin Rejection by Enhancing Neutrophil Recruitment | Immunology

Here we investigated the role of mast cells (MC) in an acute male to female skin allograft rejection model using red MC and ... Here we investigated the role of mast cells (MC) in an acute male to female skin allograft rejection model using red MC and ... They induced an early inflammatory response through degranulation and boosted local synthesis of KC, MIP-2 and TNF. This ... They induced an early inflammatory response through degranulation and boosted local synthesis of KC, MIP-2 and TNF. This ...
more infohttps://www.frontiersin.org/articles/10.3389/fimmu.2018.02690/full

Hypotension induced by vasopressin antagonists in rats: role of mast cell degranulation. | Sigma-AldrichHypotension induced by vasopressin antagonists in rats: role of mast cell degranulation. | Sigma-Aldrich

Hypotension induced by vasopressin antagonists in rats: role of mast cell degranulation.. [R A Macia, A C Silver, R A Gabel, G ... A positive correlation was found between the potency to produce edema in vivo and the potency to release mast cell histamine in ... SK&F 101926 degranulated rat peritoneal mast cells in vitro as measured by the liberation of histamine. Analogs of SK&F 101926 ... is mediated via the release of autocoids from mast cells. Serotonin appears to play a major role in mediating the ...
more infohttps://www.sigmaaldrich.com/catalog/papers/1688665

Inhibitory effects of resveratrol on human mast cell degranulation, cytokine, chemokine and leukotriene releaseInhibitory effects of resveratrol on human mast cell degranulation, cytokine, chemokine and leukotriene release

In LAD2 mast cells, both resveratrol and tranilast inhibited degranulation induced by the mast cell activators substance P, IgE ... The effects of resveratrol on mast cell activation were more marked in human primary CD34+-derived mast cells (HuMC), and the ... We investigated the effects of resveratrol on human mast cell activation in comparison to the anti-allergy drug tranilast. ... Furthermore, both resveratrol and tranilast reduced expression of the high affinity IgE receptor, FcεRI, on LAD2 cells. ...
more infohttps://www.scirp.org/journal/paperinformation.aspx?paperid=26273

Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis | ThoraxMechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis | Thorax

Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis ... Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis ...
more infohttps://thorax.bmj.com/content/74/5/455.alerts

Cell-based phenotypic screening of mast cell degranulation unveils kinetic perturbations of agents targeting phosphorylation. |...Cell-based phenotypic screening of mast cell degranulation unveils kinetic perturbations of agents targeting phosphorylation. |...

Cell-based phenotypic screening of mast cell degranulation unveils kinetic perturbations of agents targeting phosphorylation.. ... Stat3 phosphorylation has been widely reported as a key step in mast cell degranulation. Interestingly, our TCRP results showed ... Mast cells play an essential role in initiating allergic diseases. The activation of mast cells are controlled by a complicated ... In this work, we used a method named Time-dependent cell responding profile (TCRP) to track the process of mast cell ...
more infohttps://www.sigmaaldrich.com/catalog/papers/27502076

Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and...Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and...

MC degranulation was assessed by flow cytometric analysis of CD107a cell surface expression on GFP+ (transfected) cells. ... Dead cells were excluded by propidium iodide staining. FcεRI-induced degranulation in control-transfected cells (empty vector ... MC degranulation was assessed by flow cytometric analysis of CD107a cell surface expression. Transfected cells were identified ... The role of actin microfilaments in the down-regulation of the degranulation response in RBL-2H3 mast cells. J. Immunol. 162: ...
more infohttp://jem.rupress.org/content/208/9/1777

Polyclonal Antibody Immunofluorescence Immunocytochemistry Actin Dynamics to Polyclonal Antibody Flow Cytometry Mast Cell...Polyclonal Antibody Immunofluorescence Immunocytochemistry Actin Dynamics to Polyclonal Antibody Flow Cytometry Mast Cell...

Polyclonal Antibody Flow Cytometry Mast Cell Degranulation Polyclonal Antibody Flow Cytometry Mast Cell Degranulation: ... Polyclonal Antibody Glial Cell Migration Polyclonal Antibody Glial Cell Migration: Polyclonal Antibody - β-Catenin Antibody, ... 2019 Cell Signaling Technology, Inc. All Rights Reserved.. Email: [email protected] ... Antibody Immunofluorescence Immunocytochemistry Actin Dynamics to Polyclonal Antibody Flow Cytometry Mast Cell Degranulation ...
more infohttps://www.cellsignal.com/1/4/indexd27.html

Mast cell degranulation - a mechanism for the anti-arrhythmic effect of endothelin-1?  - StrathprintsMast cell degranulation - a mechanism for the anti-arrhythmic effect of endothelin-1? - Strathprints

Walsh, S.K. and Kane, K.A. and Wainwright, C.L. (2009) Mast cell degranulation - a mechanism for the anti-arrhythmic effect of ... In sham animals ET-1 and compound 48/80 both induced mast cell degranulation (P , 0.001), an effect which was abolished by DSCG ... Mast cell degranulation - a mechanism for the anti-arrhythmic effect of endothelin-1? ... After 30 min of CAO, the hearts were removed and mast cell degranulation determined by histological analysis. A parallel series ...
more infohttps://strathprints.strath.ac.uk/19091/

Interplay between Affinity and Valency in Effector Cell Degranulation: A Model System with Polcalcin Allergens and Human...Interplay between Affinity and Valency in Effector Cell Degranulation: A Model System with Polcalcin Allergens and Human...

... resulting in cell degranulation and release of proinflammatory mediators. The extent of effector cell activation is linked to ... Our results indicate that polcalcin multimers are required to stimulate high levels of effector cell degranulation when using ... Interplay between Affinity and Valency in Effector Cell Degranulation: A Model System with Polcalcin Allergens and Human ... Interplay between Affinity and Valency in Effector Cell Degranulation: A Model System with Polcalcin Allergens and Human ...
more infohttps://www.jimmunol.org/content/203/7/1693

VAAT regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivoVAAT regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo

1. Mechanisms triggering the recruitment of mast cell progenitors to the lung and regulation of mast cell degranulation. Open ... VAAT regulates IgE-mediated mast cell degranulation in vitro and mast cell-mediated reactions in vivo. Pettersson, Hanna ... Mechanisms triggering the recruitment of mast cell progenitors to the lung and regulation of mast cell degranulation. Zarnegar ... some influenza-induced mast cell progenitors developed into an intermediate mast cell stage before they matured into mast cells ...
more infohttp://uu.diva-portal.org/smash/record.jsf?pid=diva2:1040933

Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to...Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to...

Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to ... We investigated the ability of MRGPRX2 ligands to induce degranulation in rat basophilic leukemia-2H3 cells individually ... Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to ... Naturally Occurring Missense MRGPRX2 Variants Display Loss of Function Phenotype for Mast Cell Degranulation in Response to ...
more infohttp://www.jimmunol.org/content/201/2/343

Inserm - Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulationInserm - Tomosyn functions as a PKCδ-regulated fusion clamp in mast cell degranulation

... inhibited FcεRI-stimulated degranulation of mast cells. After mast cell activation, tomosyn-1 was phosphorylated on serine and ... Mast cells rely on SNARE-mediated membrane fusion for degranulation stimulated by crosslinking of immunoglobulin E (IgE) bound ... Our findings identified tomosyn-1 as an inhibitor of mast cell degranulation that required PKCδ to switch its interaction with ... Incubation with high IgE concentrations increased tomosyn-1 abundance in cultured mast cells. Similarly, in basophils from ...
more infohttps://www.hal.inserm.fr/inserm-02323254

A Neurotensin Receptor Antagonist Inhibits Acute Immobilization Stress-Induced Cardiac Mast Cell Degranulation, a Corticotropin...A Neurotensin Receptor Antagonist Inhibits Acute Immobilization Stress-Induced Cardiac Mast Cell Degranulation, a Corticotropin...

... mast cell mast cell degranulation from 50 ± 9% to 28 ± 3% (n = 5 rats, 6405 mast cells counted), indicating that cardiac ... NRS had no effect (P = .03 compared to control) on mast cell degranulation which was 54 ± 6% (n = 3 rats, 2704 mast cells ... 3A and B), only few of which showed signs of degranulation. In many mast cells from stressed animals, however, degranulation ... 1998) Stem cell factor in mast cells and increased mast cell density in idiopathic and ischemic cardiomyopathy. Circulation 97: ...
more infohttp://jpet.aspetjournals.org/content/287/1/307

A Microplate Assay to Assess Chemical Effects on RBL-2H3 Mast Cell Degranulation: Effects of Triclosan without Use of an...A Microplate Assay to Assess Chemical Effects on RBL-2H3 Mast Cell Degranulation: Effects of Triclosan without Use of an...

Naal, R., Tabb, J., Holowka, D., Baird, B. In situ measurement of degranulation as a biosensor based on RBL-2H3 mast cells. ... Demo, S. D., et al. Quantitative measurement of mast cell degranulation using a novel flow cytometric annexin-V binding assay. ... Hutchinson, L. M., et al. Inorganic arsenite inhibits IgE receptor-mediated degranulation of mast cells. J. Appl. Toxicol. 31, ... Seldin, D. C., et al. Homology of the rat basophilic leukemia-cell and the rat mucosal mast-cell. Proc. Natl. Acad. Sci. U.S.A ...
more infohttps://www.jove.com/video/50671/organik-solvent-kullanm-olmadan-triklosan-etkileri-rbl-2h3-mast-hcre?language=Turkish

Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles...Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles...

Increased mast cell degranulation and co-localization of mast cells with the NMDA receptor-1 during healing after Achilles ... Cell and Tissue Research On the subject. Cell and Molecular Biology Search outside of DiVA. GoogleGoogle Scholar. ... Three weeks after rupture, histological quantification of mast cell numbers and their state of degranulation was assessed by ... An increased number of mast cells and a higher proportion of degranulated mast cells were found in the healing Achilles tendon ...
more infohttp://liu.diva-portal.org/smash/record.jsf?pid=diva2%3A1165632&c=27&searchType=ORGANISATION&language=en&query=&af=%5B%5D&aq=%5B%5B%7B%22organisationId%22%3A%22877703%22%7D%5D%5D&aq2=%5B%5B%5D%5D&aqe=%5B%5D&noOfRows=50&sortOrder=author_sort_asc&sortOrder2=title_sort_asc&onlyFullText=false&sf=all

Cromolyn administration (to block mast cell degranulation) reduces necrosis of dystrophic muscle in mdx mice, Neurobiology of...Cromolyn administration (to block mast cell degranulation) reduces necrosis of dystrophic muscle in mdx mice, Neurobiology of...

... to block mast cell degranulation) reduces necrosis of dystrophic muscle in mdx mice, Neurobiology of Disease" on DeepDyve, the ... Cromolyn administration (to block mast cell degranulation) reduces necrosis of dystrophic muscle in mdx mice. Radley, Hannah G. ... We hypothesise that blockade of mast cell degranulation would reduce the extent of myofibre necrosis in the mdx mouse. Daily ... We hypothesise that blockade of mast cell degranulation would reduce the extent of myofibre necrosis in the mdx mouse. Daily ...
more infohttps://www.deepdyve.com/lp/elsevier/cromolyn-administration-to-block-mast-cell-degranulation-reduces-wCySz0bzDh?impressionId=5c71d5918ed10&i_medium=docview&i_campaign=references&i_source=references
  • Similarly, the sera from patients treated with OmAb in the context of the clinical trial who had a good clinical outcome maintained the capacity to activate mast cells and basophils. (cun.es)
  • Concomitantly, CPT-11 enhanced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels and inducible nitric oxide synthase (iNOS) gene expression, associated with an increase in the total number macrophages (positive cells for ionized calcium-binding adapter molecule, Iba-1) and degranulated mast cells in the small intestine segments and caused significant weight loss. (nih.gov)
  • Our data suggests the participation of mast cells on the CPT-11-induced intestinal mucositis, macrophages activation, enteric reactive gliosis, and neuron loss. (nih.gov)
  • In AOM, macrophages were the predominant cell in PF, while in pars tensa (PT), polymorphonuclear cells (mainly neutrophils) predominated. (diva-portal.org)
  • 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. (frontiersin.org)
  • We investigated the effects of resveratrol on human mast cell activation in comparison to the anti-allergy drug tranilast. (scirp.org)
  • The effects of resveratrol on mast cell activation were more marked in human primary CD34+-derived mast cells (HuMC), and the polyphenol was significantly more efficacious than tranilast in these cells. (scirp.org)
  • In conclusion, resveratrol inhibited key aspects of human mast cell activation to physiological stimuli, and was comparable, if not more efficacious than the anti-allergy drug tranilast. (scirp.org)
  • The extent of effector cell activation is linked to allergen affinity, oligomeric state, valency, and spacing of IgE-binding epitopes on the allergen. (jimmunol.org)
  • One of the problems I have been tentatively diagnosed with in the last few years is mastocytosis , or a mast cell activation disorder (MCAD). (blogspot.com)
  • Complementation of p110γ null mast cells with p101 and p110γ restored the activation of Akt and cell migration, but failed to support degranulation. (sciencemag.org)
  • The clustering of the intracellular domains of the cell-bound Fc receptors, which are associated with the cross-linked IgE molecules, causes a complex sequence of reactions inside the mast cell that lead to its activation. (wikipedia.org)
  • It was previously shown that acute psychological stress by immobilization results in dura mast cell degranulation, an effect blocked by pretreatment with antiserum against corticotropin-releasing hormone (CRH). (aspetjournals.org)
  • This effect was inhibited by pretreatment with the "antiallergic" drug sodium cromoglycate (cromolyn), which is thought to act primarily through mast cell stabilization. (aspetjournals.org)
  • These results demonstrate for the first time that when given prior to ischaemia ET-1 mediates its anti-arrhythmic effects, at least in part, via cardiac mast cell degranulation. (strath.ac.uk)
  • Our results demonstrate a nonredundant function for the p101 and p84 PI3Kγ adaptor proteins and show that distinct pools of PtdIns(3,4,5)P 3 at the plasma membrane can elicit specific cell responses. (sciencemag.org)
  • RESULTS: Degranulation of the mast cells occurred within 3 hours of applying compound 48/80. (diva-portal.org)
  • Here we investigated the role of mast cells (MC) in an acute male to female skin allograft rejection model using red MC and basophil (RMB) mice enabling conditional MC depletion. (frontiersin.org)
  • It has not been explored whether CPT-11 is able to alter the enteric glial and neuronal cell, and the role of mast cells in this effect. (nih.gov)
  • Therefore, this study was conducted to investigate the effect of CPT-11 on the enteric glial and neuronal cells, as well as to study the role of mast cells in the CPT-11-induced intestinal mucositis. (nih.gov)
  • Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and blood-brain barrier function. (wikipedia.org)
  • Because the recruitment of mast cell progenitors started early after influenza infection, the role of innate immune signals in inducing the recruitment of mast cell progenitors was addressed. (diva-portal.org)
  • I definitely showed autoimmune issues in my blood tests there, but the tryptase levels (used to measure the leakiness of the immature mast cells) were in normal range. (blogspot.com)
  • The site an immature mast cell settles in probably determines its precise characteristics. (wikipedia.org)
  • Importantly, knockdown of CD107a/LAMP-1 in primary human natural killer (NK) cells and deficiency of CD107a/LAMP-1 in mice resulted in increased NK cell apoptosis upon target cell-induced degranulation. (nih.gov)
  • It is known that mast cell degranulation depends upon membrane anchored SNAREs (soluble N-ethylmaleidimide-sensitive factor attachment protein receptors) and accessory proteins that form the trans-SNARE complex, a 4 helical bundle central to exocytic fusion. (usm.edu)
  • To investigate the properties of the degranulation related trans-SNARE complex, we decided to create a C-terminal truncation mutant of SNAP-23, which would arrest membrane fusion after the formation of the 4-helical bundle. (usm.edu)
  • Tympanic membrane, mast cells, otitis media. (diva-portal.org)
  • Complement proteins can activate membrane receptors on mast cells to exert various functions as well. (wikipedia.org)
  • Light and electron microscopic studies of the endothelium of postcapillary venules at sites of DTH revealed the development of gaps between adjacent cells. (rupress.org)