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 aim of the present study was to create clearly documented immediate-type allergy to food protein in the intestine of rats and to study some pathophysiological phenomena induced by challenge with the allergen. To achieve this, rats were sensitized with ovalbumin. A passive cutaneous anaphylaxis reaction to ovalbumin was negative in all controls and positive in all test animals when Bordetella pertussis was used as adjuvant. Sixty minutes after an intravenous injection of 125I-human serum albumin and 45 min after an ovalbumin challenge, given by gavage, the rats were sacrificed. The intestine was removed and sections taken for morphologic studies. The remainder was rinsed, opened, cut into measured segments, weighed, and the radioactivity was measured. Disaccharidases, alkaline phosphatase, and protein were estimated in homogenates of epithelium. Results in both control and test animals showed that radioactivity decreased as one moved distally along the intestine. However, radioactivity was significantly higher (p less than 0.01) in the intestine of test animals than in controls. Radioactivity in liver, kidney, spleen, and lungs was identical in test and control animals. There was significant reduction in levels of alkaline phosphatase (p varied from less than 0.05 to less than 0.001), maltase (p less than 0.05), and sucrase (p less than 0.05 to less than 0.01). Lactase activity in contrast was significantly raised (p less than 0.05). There was no change in intestinal morphology or in the intestinal mast cell count.
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PMID:The effect of immediate-type gastrointestinal allergic reactions on brush border enzymes and gut morphology in the rat. 392 23

Passive cutaneous anaphylaxis (PCA) produced by antigen challenge to antibody-sensitized rats were interfered with by prior treatment with pertussis toxin, an islet-activating protein (IAP). The degree of interference was dependent on the dose and injection time of IAP; the effect of IAP developed slowly, with a maximal effect being observed 3 days later. Inhibition of PCA by IAP was associated with a decrease in histamine release from peritoneal mast cells, making it very likely that the process affected was mast cell secretion. Much less histamine was discharged in vitro, in response to certain membrane receptor (e.g. IgE receptor) stimulation, from mast cells that had been exposed to IAP than from the cells not exposed. Such an inhibitory effect of IAP was not observed when histamine release was provoked by a calcium ionophore without mediation of membrane receptors. IAP was a stronger inhibitor of histamine release than beta-adrenergic agonists. Further inhibition was produced when a beta-agonist was added to IAP-treated mast cells. The increase in the cellular content of cyclic AMP was associated with beta-agonist-induced, but not with IAP-induced, inhibition of histamine release. Thus, IAP inhibited histamine release by a mechanism in which metabolism of cyclic AMP was not directly involved.
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PMID:Suppression of passive cutaneous anaphylaxis by pertussis toxin, an islet-activating protein, as a result of inhibition of histamine release from mast cells. 614 11

An association was found in rats of different strains between the susceptibility to EAU and the number of mast cells in the choroid of the eye. High responder rats (Lewis, CAR) had strikingly more choroidal mast cells than the low responder BN animals, whereas intermediate numbers of mast cells were found in the F1 hybrids of Lewis and BN (LBNF), which exhibited an average level of susceptibility to EAU. LeR rats, derived from the Lewis strain, developed EAU only when treated with B. pertussis, and their number of choroidal mast cells was only about 1/5 of that found in the Lewis rats. Unlike the differences in the number of choroidal mast cells, small variations were found in the skin mast cell numbers of the tested rats. It is proposed that the number of local mast cells may be one mechanism by which the susceptibility to an organ-specific autoimmune disease is genetically regulated.
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PMID:An association between susceptibility to experimental autoimmune uveitis and choroidal mast cell numbers. 633 30

PVG/c inbred rats were sensitized by intra-peritoneal injection of DNP 19-ovalbumin with or without heat-killed Bordetella pertussis as adjuvant. The use of adjuvant was associated with a greater serum IgE, greater cutaneous immediate hypersensitivity, but no increase in immediate pulmonary reactivity to aerosol challenge. The number of mast cells in the trachea of adjuvant-sensitized rats was significantly reduced when compared with both unsensitized and allergen sensitized rats but this reduction in mast cell number did not occur in the skin. The reduction in tracheal and possibly other airway mast cells may explain the failure of the adjuvant sensitized rats to show increased pulmonary reactivity despite the increased serum IgE. The B. pertussis may have acted on the mediastinal lymph nodes, which drain both the peritoneal cavity and the lungs, to produce the observed reduction in tracheal mast cells.
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PMID:Reduced tracheal mast cell numbers in adjuvant-sensitized rats associated with reduced pulmonary reactivity. 742 32

The common pathway of heterogenous mast cell activation as mediated by antigens is through the cross-linking of IgE bound to Fc epsilon RI receptors. The peptidergic pathway of mast cell activation, achieved by cationic secretagogues, is restricted to "serosal" mast cells, the experimental models being rat peritoneal and human skin mast cells. Cationic secretagogues include positively charged peptides but also various amines such as compound 48/80 and natural polyamines. An early intracellular event of this pathway is the activation of pertussis toxin-sensitive G proteins. The correlation observed between the ability of basic compounds to trigger mast cell exocytosis and their potency to activate purified G proteins strongly suggests that cationic compounds activate mast cell G proteins via a receptor-independent but membrane-assisted process. In this paper, alternative mechanisms are discussed. The consequence of G protein stimulation is the activation of phospholipase C with an increase in inositol triphosphates. Natural polyamines are relatively poor triggers of mast cells (10(-4) to 10(-2) M). Neuropeptides such as substance P, neuropeptide Y or vasoactive intestinal peptide, peptidic hormones such as kinins, and venoms such as mastoparan and mast cell degranulating peptide, are all active in a concentration range from 10(-7) to 10(-4) M. The cationic anaphylatoxin C3a also stimulates mast cells at concentrations below precursor complement C3 blood levels. The component C3 of the complement system is one of only a few plasma proteins having activation fragments (i.e. C3a) that can be generated at micromolar levels. The effects of basic secretagogues defines a peptidergic pathway of mast cell activation, which represents a potentially toxic process considering the tissue effects caused by exogenous basic compounds such as venom peptides and certain amine containing drugs. Peptidergic activation of mast cells may also be a pathophysiological process having an important role in neurogenic inflammation and in diseases involving extensive activation of the blood complement cascade.
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PMID:Peptidergic pathway in human skin and rat peritoneal mast cell activation. 751 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

Recent evidence suggests that peptides induce the release of mediators from rat peritoneal mast cell by means of a receptor-independent mechanism, possibly involving an interaction with sialic acid residues at the cell surface followed by the activation of a guanine nucleotide binding protein (G protein). We have now examined the potential involvement of sialic acid residues and of G protein stimulation in the activation of both human and rat cutaneous mast cells by neuropeptide Y, its C-terminal fragments and the wasp venom peptide, mastoparan. Neuropeptide Y-(18-36) was the most effective histamine releaser of the fragments tested, the order of potency being neuropeptide Y-(18-36) > neuropeptide Y-(22-36) > neuropeptide Y-(1-36). This order of potency suggests that the effects of the peptides are not mediated through classical NPY receptors. The hydrolysis of sialic acid residues by neuraminidase and the inhibition of G proteins by benzalkonium chloride or pertussis toxin significantly inhibited the secretory response of cutaneous mast cells to neuropeptide Y-(18-36) and mastoparan. These results demonstrate that the peptidergic pathway described for the activation of peritoneal rat mast cells is also involved in the response of cutaneous human and rat mast cells to peptides.
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PMID:Human and rat cutaneous mast cells: involvement of a G protein in the response to peptidergic stimuli. 753 61

Mast cells accumulate at sites of angiogenesis. The factor(s) that control mast-cell recruitment at these sites have yet to be defined. We sought to determine if angiogenic factors result in mast-cell chemotaxis. In this study, we observed that platelet-derived growth factor-AB (PDGF-AB), vascular endothelial cell growth factor (VEGF), and basic fibroblast growth factor (bFGF) each cause directed migration of murine mast cells at picomolar concentrations, with a typical bell-shaped dose-response curve. Another potent angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF), appears to promote chemokinesis of mast cells, whereas tumor necrosis factor-alpha, a weak angiogenic factor, is less robust but still functions as a mast cell chemotactic factor. Epidermal growth factor (EGF), a growth factor with minimal angiogenic properties, was ineffective as a mast cell chemotactic factor. A checkerboard analysis confirmed the directional chemotactic response of PDGF-AB, VEGF, and bFGF, while indicating the chemokinetic response induced by PD-ECGF. Cross-desensitization of growth-factor-induced directed migration was observed between PDGF-AB and bFGF, and also between PDGF-AB and PD-ECGF. Tyrosine kinase-inhibitor genistein effectively dampened the chemotactic responses, whereas pertussis toxin had no effect. In summary, our findings suggest that factors known to act on endothelial cells and stimulate neovascularization may simultaneously serve to recruit mast cells to these sites. The local accumulation of mast cells is believed to facilitate new vessel formation through complex cell:cell interactions.
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PMID:Angiogenic factors stimulate mast-cell migration. 754 57

We have previously demonstrated that snake venom phospholipases A2 (PLA2s) and mammalian PLA2s induced inflammatory processes. This effect was correlated with the activity of the enzymes and the release of lipid mediators. We have now determined the role of lysophosphatidylserine (LysoPS) as an inflammatory lipid mediator. Thus, we have studied the possibility that intracellular calcium concentration, phosphoinositide hydrolysis, and the subsequent histamine release in mast cells is due to the action of lysophosphatidylserine. Lysophosphatidylserine-stimulated release of histamine was significantly higher than release by other lysophospholipids. The contribution of increased phospholipase C activity and the intracellular Ca2+ influx were therefore examined. LysoPS increased mast cell calcium concentration, and this increment was associated with phospholipase C activation and release of inositol phosphates. The increase in intracellular calcium and histamine degranulation induced by LysoPS were inhibited by apomorphine. Pretreatment of mast cells with pertussis toxin decreased the secretagogic effect of LysoPS and compound 48/80 without modifying the effect of the ionophore A23187. These results suggest that pertussis toxin-sensitive G-protein might be involved in the mast cell degranulation produced by lysophosphatidylserine and allow the increase in phospholipase C activity, thus enhancing intracellular calcium concentration, which then induces exocytosis of histamine.
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PMID:Ca2+ influx, phosphoinositide hydrolysis, and histamine release induced by lysophosphatidylserine in mast cells. 755 12

Adenosine potentiates mast cell activation, but the receptor type and molecular mechanisms involved have not been defined. We, therefore, investigated the effects of adenosine on the human mast cell line HMC-1. Both the A2a selective agonist CGS21680 and the A2a/A2b nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA) increased cAMP, but NECA was fourfold more efficacious and had a Hill coefficient of 0.55, suggesting the presence of both A2a and A2b receptors. NECA 10 microM evoked IL-8 release from HMC-1, but CGS21680 10 microM had no effect. In separate studies we found that enprofylline, an antiasthmatic previously thought to lack adenosine antagonistic properties, is as effective as theophylline as an antagonist of A2b receptors at concentrations achieved clinically. Both theophylline and enprofylline 300 micro completely blocked the release of IL-8 by NECA. NECA, but not CGS21680, increases inositol phosphate formation and intracellular calcium mobilization through a cholera and pertussis toxin-insensitive mechanism. In conclusion, both A2a and A2b receptors are present in HMC-1 cells and are coupled to adenylate cyclase. In addition, A2b receptors are coupled to phospholipase C and evoke IL-8 release. This effect is blocked by theophylline and enprofylline, raising the possibility that this mechanism contributes to their antiasthmatic effects.
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PMID:Adenosine A2b receptors evoke interleukin-8 secretion in human mast cells. An enprofylline-sensitive mechanism with implications for asthma. 756 91


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