Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The histamine release induced by compound 48/80, bradykinin or polyethylenimine with a molecular weight of 600 (PEI6) was inhibited by wheat germ agglutinin (WGA) and phytohemagglutinin E-subunits (PHA-E4), and the inhibition was specifically reversed by N-acetyl glucosamine and N-acetyl galactosamine, respectively. Concanavalin A (Con A) and phytohemagglutinin L-subunits (PHA-L4) did not inhibit the histamine release induced by compound 48/80, bradykinin or PEI6. The histamine release induced by substance P was also inhibited sugar-specifically by WGA and PHA-E4. The binding sites for compound 48/80, bradykinin, PEI6 and substance P, therefore, seemed to especially overlap each other. These binding sites were found to be glycoproteins having affinities to WGA and PHA-E4, but not to Con A and PHA-L4. The binding of WGA and PHA-E4 to the glycoproteins resulted in inhibition of the interaction between the basic secretagogues including bradykinin and substance P and their binding sites on the mast cells. The bindings of five lectins to mast cell glycoproteins were examined by lectin-blotting. Several glycoproteins, which had specific affinities to WGA and PHA-E4, but not to Con A and PHA-L4 were detected. We assumed that the binding sites for basic secretagogues which are coupled with histamine-releasing mechanisms exist among these glycoproteins. A 41-kDa protein (alpha-subunit of pertussis toxin-sensitive G protein) was not detected by WGA, suggesting that the binding sites for the basic secretagogues were not G proteins.
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PMID:Sugar-specific inhibitory effects of wheat germ agglutinin and phytohemagglutinin-E4 on histamine release induced by basic secretagogues from rat peritoneal mast cells and their possible action sites. 172 87

The synthesis and intracellular expression of glycosphingolipids by mouse serosal mast cells (SMC) have been characterized by radiolabeling and TLC and by immunodetection in situ. Chromatographic analysis of purified glycosphingolipids from SMC intrinsically labeled with [14C]galactose and [14C]glucosamine hydrochloride revealed the predominant synthesis of only the simplest neutral glycosphingolipid and ganglioside, glucosylceramide and ganglioside GM3, respectively. Intracellular indirect immunofluorescence staining of permeabilized SMC demonstrated the absence of the more complex neutral glycosphingolipids lactosylceramide, globotriosylceramide, globotetraosylceramide, and globopentaosylceramide, the absence of ganglioside GM1, and the presence of ganglioside GM3. By contrast, permeabilized mouse IL-3-dependent bone marrow culture-derived mast cells (BMMC) and mast cells recovered after 21 days of coculture of BMMC with mouse 3T3 fibroblasts expressed lactosylceramide, globotriosylceramide, globotetraosylceramide, ganglioside GM1, and ganglioside GM3, but not globopentaosylceramide intracellularly as determined by immunofluorescence. The findings indicate a loss of biosynthetic capacity and epitope maintenance for glycosphingolipids with in vivo differentiation of SMC from IL-3-dependent BMMC progenitors. Thus, although mast cells derived after coculture of these progenitors for 21 days with fibroblasts assume multiple SMC-like properties in terms of their histochemical staining and their secretory granule proteoglycan and neutral protease constituents, they do not lose the ability to express complex glycosphingolipids. The finding that glycosphingolipid composition does not change coordinately with other secretory granule markers defines a new stage of mouse mast cell development between the BMMC and SMC and provides evidence that mast cell development is more complex than previously appreciated.
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PMID:Mast cell heterogeneity. Differential synthesis and expression of glycosphingolipids by mouse serosal mast cells as compared to IL-3-dependent bone marrow culture-derived mast cells before or after coculture with 3T3 fibroblasts. 220 Aug 24

Human nasal turbinates were cultured in the presence of 3H-glucosamine, which is incorporated into nasal mucous glycoproteins. Nasal mucous glycoprotein was then characterized biochemically, and the effects of various neurohormones and immunologic stimulation on mucous glycoprotein release were analyzed. Fractionation of nasal mucous glycoprotein by gel filtration chromatography revealed a molecular size range of 2 to 200 X 10(5) (as judged by protein markers) but displayed a single, acidic charge, as reflected both in a narrow elution pattern from DEAE-cellulose and a sharp isoelectric focusing point of 2.6. Highly enriched nasal mucous glycoprotein preparations consisted of 80 per cent carbohydrate and 20 per cent protein (by weight) and included enzymatically cleavable carbohydrate side chains with molecular weights of 1,600 to 1,800. Thus, nasal mucous glycoproteins are a family of molecules that express uniform acidic charge characteristics and a wide range of molecular sizes. Cholinergic stimulation of atropine-inhibitable muscarinic receptors increased nasal mucous glycoprotein release in a dose-related manner, as did alpha-adrenergic stimulation. However, beta-adrenergic stimulation did not affect mucous glycoprotein release. Immunologic stimulation of nasal mast cells by either reversed anaphylaxis or antigen challenge after passive sensitization caused both histamine release and increased mucous glycoprotein release. Thus, nasal turbinates provide an accessible source of tissue for the analysis of nasal mucus secretion and mast cell degranulation and may provide a model for the study of pharmacologic approaches to the universally experienced discomfort of rhinorrhea.
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PMID:Analysis of human nasal mucous glycoproteins. 620 99

Chrysotile asbestos interacts with mucin-secreting cells of tracheal organ cultures, causing an increase in secretion of mucin into the culture medium. This response occurs in the absence of obvious morphologic damage to tracheal epithelial cells. We speculated that asbestos-induced hypersecretion was regulated by the interaction of fibers with specific carbohydrate residues on the cell surface. To test this hypothesis, lectins, i.e., proteins with a high affinity for mono- and oligosaccharides on the plasma membrane, were added to tissues 30 min before addition of chrysotile. Secretion of mucin into the medium was then determined over a 2-hr period by using incorporation of 3H-glucosamine. Blocking of alpha-D-mannose and alpha-D-glucose residues inhibited chrysotile-induced hypersecretion (p less than 0.05), whereas lectins blocking residues of alpha-D-N-acetylgalactosamine, beta-D-N-acetylglucosamine, alpha-L-fucose and sialic acids were ineffective. Preincubation of cultures with carboxypeptidase A or phospholipase A2, but not with neuraminidase, diminished mucin secretion caused by chrysotile. To determine if the positive surface charge of chrysotile was important in interaction with mucin cells, we examined comparatively the effects of various polycations (cationic ferritin, polylysine, DEAE-dextran) and chrysotile after leaching of fibers to remove Mg2+. Although use of polycations enhanced secretion of mucin, effects were not as striking as those observed with chrysotile. In contrast, leached chrysotile failed to elicit a hypersecretory response. These results suggest the interaction of a positively charged component (presumably Mg2+) of chrysotile with glycolipids and glycoproteins containing terminal residues of alpha-D-mannose or alpha-D-glucose.
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PMID:Studies using lectins to determine mineral interactions with cellular membranes. 631 63

The N-acetyl glucosamine (GlcNAc)-specific lectin Datura stramonium agglutinin (DSA) rapidly and sugar-specifically released histamine from rat peritoneal mast cells, and pertussis toxin (IAP) inhibited it, suggesting that DSA activated mast cells via an IAP-sensitive G protein pathway. The additive effects of DSA and basic secretagogues such as compound 48/80 that activate IAP-sensitive G protein directly suggest that they shared the same mechanism of action including involvement of the IAP-sensitive G protein. Using lectin-blotting, blots of the corresponding glycoproteins detected by DSA diminished by haptenic sugar or pretreatment of the cells with N-glycosidase F, suggesting that the binding of DSA was responsible for the mast cell activation. The other GlcNAc-specific lectins such as Phytolacca americana mitogen, Solanum tuberosum agglutinin and wheat germ agglutinin (WGA) inhibited the histamine release induced by DSA, suggesting that these lectins were antagonists, but DSA was an agonist. Sialic acid-specific Macckia amurensis mitogen (MAM) inhibited the histamine release, and neuraminidase-treatment decreased mast cell activation induced by DSA. At least four mast cell glycoproteins that have affinity to DSA, WGA and MAM and are sensitive to neuraminidase-treatment were detected by lectin-blotting. Some of them may be binding sites coupled to histamine release including the IAP-sensitive G protein pathway. DSA is a useful tool for studying signal transduction of mast cells including the involvement of the IAP-sensitive G protein.
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PMID:Datura stramonium agglutinin released histamine from rat peritoneal mast cells that was inhibited by pertussis toxin, haptenic sugar and N-acetylglucosamine-specific lectins: involvement of glycoproteins with N-acetylglucosamine residues. 753 33

A confocal fluorescence microscope using fluo-3 and 9-(dicyanovinyl)- julolidine (DCVJ) was used to study the mast cell activation by the N-acetyl glucosamine oligomer specific lectin Datura stramonium agglutinin (DSA) and inhibition by antagonist lectins having affinity to N-acetyl glucosamine (GlcNAc). DSA induced a transient increase in intracellular free calcium concentration ([Ca2+]i) followed by cytoskeletal disassembly and reassembly in rat peritoneal mast cells. These changes induced by DSA resulted in histamine release. The time course of fluorescence intensity in mast cells loaded with fluo-3- or DCVJ and activated by DSA resembled those activated by the basic polymer compound 48/80. Inhibition of [Ca2+]i rise by antagonist lectins was responsible for the inhibition of cytoskeletal assembly and the consequent histamine release induced by DSA. At the level of the individual cell, a mast cell stimulated by DSA responds in an all-or-none fashion. DSA possible induced intracellular calcium mobilization and cytoskeletal change by recognizing the GlcNAc-oligomer residues of specific glycoproteins of mast cells.
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PMID:An initial signal of activation of rat peritoneal mast cells stimulated by Datura stramonium agglutinin: a confocal fluorescence microscopic analysis of intracellular calcium ion and cytoskeletal assembly. 753 34

We determined the effects of immobilization stress on rat colonic mucus release and mast cell degranulation and examined whether corticotropin releasing factor (CRF) was involved in these responses. After 30-min immobilization, rats were killed, colonic mucosal explants were cultured, and levels of rat mast cell protease II (RMCP II) and prostaglandin E2 (PGE2) were measured. Mucin release from explants was assayed by incorporation of [3H]glucosamine into colonic mucin and by histological evaluation of goblet cell depletion. Stress caused significant increases of colonic RMCP II, PGE2, and mucin release and fecal pellet output and caused an approximately 10-fold increase in colonic mucosal levels of cyclooxygenase-2 (COX-2) mRNA. These stress-associated changes were reproduced by intravenous or intracerebral injection of CRF in conscious, nonstressed rats. Pretreatment of rats with the CRF antagonist alpha-helical-CRF9-41, hexamethonium, atropine, or bretylium, or the mast cell stabilizer lodoxamide inhibited stress-induced release of RMCP II, PGE2, and mucin, whereas indomethacin prevented mucin release but not mast cell degranulation. Hexamethonium and CP-96,345, a substance P antagonist, inhibited fecal pellet output caused by stress. We conclude that CRF released during immobilization stress increases colonic transit via a neuronal pathway and stimulates colonic mucin secretion via activation of neurons and mast cells.
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PMID:Acute stress causes mucin release from rat colon: role of corticotropin releasing factor and mast cells. 894 4

The selectins are calcium-dependent C-type lectins that bind certain sialylated, fucosylated, sulfated glycoprotein ligands. L-selectin also recognizes endothelial proteoglycans in a calcium-dependent manner, via heparan sulfate (HS) glycosaminoglycan chains enriched in unsubstituted glucosamine units. We now show that these HS chains can also bind P-selectin, but not E-selectin. However, while L-selectin binding requires micromolar levels of free calcium, P-selectin recognition is largely divalent cation-independent. Despite this, HS chains bound to P-selectin are eluted by ethylenediamine tetraacetic acid (EDTA), but only at high concentrations. Porcine intestinal mucosal (mast cell-derived) heparin (PIM-heparin) shows similar properties, with no binding to E-selectin, calcium-dependent binding of a subfraction to L-selectin and to P-selectin, and calcium-independent binding of a larger fraction to P-selectin, the latter being disrupted by high EDTA concentrations. Analysis of defined heparin fragment pools shows a size dependence for interaction, with tetradecasaccharides showing easily detectable binding to L- and P-selectin affinity columns. L-selectin binding fragments include more heavily sulfated and epimerized regions and, as with the endothelial HS chains, they are enriched in free amino groups. The P-selectin binding component includes this fraction as well as some less highly modified regions. Thus, endothelium-derived HS chains and mast cell-derived heparins could play a role in modulating the biology of selectins in vivo. Notably, P- and L-selectin binding to sialyl-Lewisx and to HL-60 cells (which are known to carry the native ligand PSGL-1) is inhibited by unfractionated pharmaceutical heparin preparations at concentrations 12-50-fold lower than those recommended for effective anticoagulation in vivo. In contrast, two low molecular weight heparins currently considered as clinical replacements for unfractionated heparin are much poorer inhibitors. Thus, patients undergoing heparin therapy for other reasons may be experiencing clinically significant inhibition of L- and P-selectin function, and the current switchover to low-molecular weight heparins may come at some loss of this effect. Low-dose unfractionated heparin should be investigated as a treatment option for acute and chronic diseases in which P- and L-selectin play pathological roles.
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PMID:Differential interactions of heparin and heparan sulfate glycosaminoglycans with the selectins. Implications for the use of unfractionated and low molecular weight heparins as therapeutic agents. 946 83

The purpose of this study was to determine the effects of mast cell coculture on human orbital fibroblasts. Thyroid-associated ophthalmopathy is characterized by infiltration of lymphocytes and mast cells and connective tissue activation in the orbit, leading to a disordered accumulation of hyaluronan and intense inflammation. Here, we report that HMC-1, an established human mast cell line, can activate human orbital fibroblasts to produce increased levels of prostaglandin E2 (PGE2) and hyaluronan when cocultured. HMC-1 cells up-regulate, in these fibroblasts, the expression of PG endoperoxide H synthase-2 (EC 1.14.99.1, PGHS-2), the inflammatory cyclooxygenase. This induction, at a pretranslational level, underlies the increase in PGE2 synthesis. The up-regulation can be attenuated with dexamethasone (10 nM), and the increase in PGE2 production can be inhibited by SC 58125, a specific PGHS-2 inhibitor. Moreover, anti-interleukin-4 receptor antibodies can block prostanoid production in the fibroblasts elicited by HMC-1 cells, suggesting that this cytokine might represent a molecular conduit for mast cell/fibroblast cross-talk. HMC-1 cells also increased hyaluronan synthesis, as was evidenced by a 2-fold increase in [3H]glucosamine incorporation into the macromolecule. To our knowledge, these findings are the first demonstrating the ability of mast cells to activate orbital fibroblasts, and the findings suggest a potential role for these cell-cell interactions in the pathogenesis of thyroid-associated ophthalmopathy.
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PMID:HMC-1 mast cells activate human orbital fibroblasts in coculture: evidence for up-regulation of prostaglandin E2 and hyaluronan synthesis. 1043 7

Following a fortuitous observation that migraine headaches ceased in a patient receiving glucosamine therapy for osteoarthritis, a further ten patients with migraine or migraine-like vascular headaches, refractory to established preventive or abortive therapies, have been treated with daily oral glucosamine. After a lag of 4-6 weeks, a substantial reduction in headache frequency and/or intensity has been noted; in some cases, the benefit appears to be dose-dependent. Since glucosamine can be a rate-limiting precursor for mucopolysaccharide synthesis, it is germane to note previous reports that heparin and pentosan polysulfate may have migraine-preventive activity. There is reason to suspect that mast cells are central mediators of the neurogenic inflammation associated with migraine and cluster headaches. The heparin produced by mast cells may function to provide feedback down-regulation of mast cell activation, and exerts a range of other anti-inflammatory effects. We postulate that supplemental glucosamine can boost mast cell heparin synthesis - perhaps correcting a functional heparin deficiency - thereby preventing or ameliorating the neurogenic inflammation that mediates pain in vascular headache. Whether or not this idea has validity, a controlled study of glucosamine for migraine prophylaxis appears to be warranted.
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PMID:Glucosamine for migraine prophylaxis? 1098 8


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