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)

A novel plasminogen-binding protein has been isolated from human plasma utilizing plasminogen-Sepharose affinity chromatography. This protein copurified with alpha 2 antiplasmin when the plasminogen affinity column was eluted with high concentrations of epsilon-aminocaproic acid (greater than 20 mM). Analysis by sodium dodecyl sulfate suggests this protein has an apparent Mr of 60,000. The amino-terminal amino acid sequence showed no similarity to other protein sequences. Based on the amino-terminal amino acid sequence, oligonucleotide probes were designed for polymerase chain reaction primers, and an approximately 1,800 base pair cDNA was isolated that encodes this Mr 60,000 protein. The deduced amino acid sequence reveals a primary translation product of 423 amino acids that is very similar to carboxypeptidase A and B and consists of a 22-amino acid signal peptide, a 92-amino acid activation peptide, and a 309-amino acid catalytic domain. This protein shows 44 and 40% similarity to rat procarboxypeptidase B and human mast cell procarboxypeptidase A, respectively. The residues critical for catalysis and zinc and substrate binding of carboxypeptidase A and B are conserved in the Mr 60,000 plasminogen-binding protein. The presence of aspartic acid at position 257 of the catalytic domain suggests that this protein is a basic carboxypeptidase. When activated by trypsin, it hydrolyzes carboxypeptidase B substrates, hippuryl-Arg and hippuryl-Lys, but not carboxypeptidase A substrates, and it is inhibited by the specific carboxypeptidase B inhibitor (DL-5-guanidinoethyl)mercaptosuccinic acid. We propose that the Mr 60,000 plasminogen-binding protein isolated here is a novel human plasma carboxypeptidase B and that it be designated pCPB.
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PMID:Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma. 193 7

Air-pouch-type inflammation was induced by injecting sodium carboxymethyl cellulose solution containing leukotriene C4 (LTC4, 3.20 x 10(-7) M, 0.2 micrograms/ml) and prostaglandin E2 (PGE2, 5.68 x 10(-6) M, 2.0 micrograms/ml), platelet-activating factor (PAF, 1 x 10(-6) M, 0.52 micrograms/ml), or 12-O-tetradecanoyl phorbol 13-acetate (TPA, 1.62 x 10(-6) M, 1.0 micrograms/ml) into an air pouch made on the dorsum of rats. Vascular permeability and tissue edema formation were significantly increased by injecting the phlogogen solution. The histamine level in the pouch fluid was dramatically increased by injecting TPA but not by LTC4 and PGE2, or PAF. Injection of isoproterenol or procaterol with the phlogogen solution produced dose-dependent suppression of both vascular permeability increase and tissue edema formation. However, the TPA-induced increase in the histamine level was not suppressed in parallel with the decrease of vascular permeability or tissue edema formation. These results indicate that beta-agonists suppress vascular permeability response and local tissue edema formation not by inhibiting mast cell degranulation, but by inhibiting the reactivity of the local vasculature to chemical mediators such as arachidonate metabolites, PAF, and histamine and serotonin released from mast cells.
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PMID:Suppression by adrenoceptor beta-agonists of vascular permeability increase and edema formation induced by arachidonate metabolites, platelet-activating factor, and tumor-promoting phorbol ester TPA. 197 74

The effect of chronic hyperglycemia and polyol pathway activation on the Schwann cell has not been resolved although injury to this cell has long been suspected in diabetic neuropathy. Hyperglycemia, resulting from galactose intoxication of four months duration, induces dose-dependent accumulations of endoneurial fluid sodium and chloride that are linked to polyol pathway activity and associated with dose-dependent increases in sciatic nerve water content, endoneurial fluid pressure and (Na+, K+)-ATPase activity. In order to understand the impact of these changes on the nerve microenvironment, cellular elements of the endoneurium were quantitatively and qualitatively assessed in rats receiving 0%, 10%, 20% or 40% galactose diets. After four months of galactose intoxication, dose-dependent changes in the size distribution of myelinated nerve fibers were apparent. A shift in size-frequency histograms of galactose-intoxicated animals towards smaller fibers was accompanied by a decrease in axon diameter and the volume fraction ratio of axon to myelinated nerve fibers. In the sciatic nerve of all 40% galactose-fed rats examined by electron microscopy, Schwann cells of myelinated fibers showed both reactive and degenerative changes. Demyelination was preceded by splitting at the intraperiod line. Remyelination was identified by axons with disproportionately thin myelin sheaths. Axonal dystrophy and degeneration were infrequently seen, but there was axonal regeneration. Dose-dependent increases in mast cell number were observed with degranulation apparent in rats receiving 20% and 40% galactose. Endothelial cell number and basal lamina thickness were increased in the endoneurial vessels of galactose-intoxicated rats. Increased cytoplasmic area and degenerative changes in pericytes were also noted. These observations indicate that significant morphologic changes accompany the hyperosmotic imbalance resulting from galactose intoxication of four months duration. Schwann cell injury and demyelination are present in a disorder linked to polyol metabolism since aldose reductase, the anabolic enzyme of the polyol pathway, is localized to this myelin-forming cell.
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PMID:Cellular pathology of the nerve microenvironment in galactose intoxication. 202 66

Cromolyn sodium has been reported to inhibit hypoxic pulmonary vasoconstriction (HPV) in dogs and sheep, presumably by stabilizing mast cell membranes and thereby preventing the release of mediators such as leukotrienes. Because the effects of leukotriene synthesis and receptor blockers on HPV have been variable across studies, we studied the effect of cromolyn on HPV in the halothane-anesthetized sheep, a model in which we have found leukotriene synthesis and receptor blockers to be ineffective. In control animals, hypoxia (FIO2 = 0.13) increased pulmonary artery pressure (Ppa) 67% and pulmonary vascular resistance 85%, and these responses were reproducible with a second episode of hypoxia. In a second group of sheep, hypoxia (FIO2 = 0.13) during cromolyn administration (6 mg.kg-1.min-1) for 30 min increased (Ppa) 104% and increased pulmonary vascular resistance 124%. In a third group of sheep, cromolyn sodium (6 mg.kg-1.min-1) without hypoxia did not significantly affect pulmonary hemodynamics. We conclude that cromolyn sodium does not inhibit HPV in halothane-anesthetized sheep. In experimental designs in which cromolyn does alter HPV, the effect is more likely due to altered release of modulators of HPV rather than to decreased release of obligatory mediator of HPV.
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PMID:Cromolyn sodium does not inhibit hypoxic pulmonary vasoconstriction in sheep. 211 66

Cultured mast cells derived from murine bone marrow were investigated for the presence of specific interferon-gamma (IFN-gamma) receptors, and for the effects of IFN-gamma on mast cell proliferation. 125I-labeled recombinant IFN-gamma (125I-Mu-rIFN-gamma) was shown to bind to high-affinity receptors on these cells. Scatchard analysis of binding data indicated the presence of about 500 homogeneous binding sites per cell, with an apparent equilibrium dissociation constant of 3 X 10(-10) M. The binding of 125I-Mu-rIFN-gamma to mast cells was inhibited by unlabeled Mu-rIFN-gamma but not by unlabeled Mu-IFN-alpha/beta. Cross-linking of 125I-Mu-rIFN-gamma to mast cell membrane proteins using a cross-linking agent yielded a predominant complex of 100 +/- 10 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography which most likely represents the IFN-gamma-receptor complex. To assess the biological significance of these receptors, we studied the effects of Mu-rIFN-gamma on mast cell proliferation, which was markedly inhibited in mast cell precursors but not in mature mast cells. These in vitro results are in agreement with the antiproliferative effect of IFN-gamma previously reported for other hematopoietic progenitors, and suggest that IFN-gamma could find its application in the treatment of human systemic mastocytosis.
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PMID:Specific high-affinity receptors for interferon-gamma on mouse bone marrow-derived mast cells: inhibitory effect of interferon-gamma on mast cell precursors. 213 79

In isotonic buffer, IgE receptor-mediated exocytosis from rat basophilic leukemia cells is dependent on extracellular Ca2+, with half-maximal degranulation requiring 0.4 mM Ca2+. No significant exocytosis occurs in the absence of extracellular Ca2+. This absolute requirement for Ca2+ is eliminated by suspending the cells in a hypotonic buffer containing 60 to 80 mM K+; Na+ cannot substitute for K+. Optimal Ca2(+)-independent exocytosis occurs in a buffer containing 20 mM dipotassium Pipes, pH 7.1, 40 mM KCl, 5 mM glucose, 7 mM Mg acetate, 0.1% BSA, and 1 mM EGTA. The cells maintain this Ca2(+)-independent exocytosis even if they are preincubated with 1 mM EGTA for 40 min at 37 degrees C before triggering. Exocytosis is eliminated as isotonicity is approached by adding sucrose, NaCl, KCl, or potassium glutamate to the buffer. Quin 2 fluorescence measurements reveal only a very small rise in [Ca2+]i when the cells are triggered in hypotonic buffer in the absence of extracellular Ca2+ and the presence of 1 mM EGTA. In isotonic buffer, degranulation does not occur under conditions that lead to such a small rise in [Ca2+]i. Sustained IgE receptor-mediated phosphatidylinositol hydrolysis, which is also Ca2+ dependent in isotonic buffer, becomes independent of Ca2+ in the hypotonic buffer. In fact, the rate of phosphatidylinositol hydrolysis in hypotonic buffer in the absence of Ca2+ (and presence of 1 mM EGTA) is twice that observed in isotonic buffer in the presence of 1 mM Ca2+. These data show that in hypotonic buffer, the requirement of IgE receptor-mediated PI hydrolysis for extracellular Ca2+ is eliminated, and degranulation proceeds with a [Ca2+]i of 0.1 microM, the baseline level of [Ca2+]i found in resting cells. These results are consistent with the hypothesis that, in isotonic buffer, the Ca2+ requirement for mast cell degranulation is for the generation of second messengers via hydrolysis of membrane phosphatidylinositols.
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PMID:IgE receptor-mediated phosphatidylinositol hydrolysis and exocytosis from rat basophilic leukemia cells are independent of extracellular Ca2+ in a hypotonic buffer containing a high concentration of K+. 214 6

Basal and stimulated changes in ion transport in vitro were examined in jejunal mucosa from rats during inflammation produced after infection with the nematode Nippostrongylus brasiliensis. The gut was acutely inflamed at days 7 and 10 when net secretion of Na+ and Cl- ions was evident. Serum levels of rat mast cell protease II were elevated, providing evidence for mast cell activation. In addition, the magnitude of the short-circuit current responses to electrical transmural stimulation of enteric nerves (but not to histamine in the presence of neural blockade) were significantly reduced (p less than 0.01) to 17%-33% of control values, suggesting abnormalities of mucosal nerves. Following worm expulsion, serum levels of rat mast cell protease II and ion transport returned to normal. However, mastocytosis was apparent in gut mucosa and parasite antigen stimulated net secretion. In the absence of antigen, short-circuit current responses to nerve stimulation were increased (to 122% of controls; p less than 0.05). These findings suggest that changes in mast cells and enteric nerves occur during inflammation in this model and implicate neural and mast cell interactions with the epithelium in producing the ion-transport abnormalities.
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PMID:Ion transport abnormalities in inflamed rat jejunum. Involvement of mast cells and nerves. 215 98

We have obtained biopsy specimens of the nasal mucous membrane before and during the grass-pollen season in 22 patients with seasonal allergic rhinitis to grass pollen to assess the effects on cellular infiltration of natural exposure to allergen. Biopsy sections were examined by light microscopy, and quantitative assessment was made of numbers of mast cells and eosinophils. The patients were divided into 11 who were treated with placebo and 11 patients who were treated with topical nedocromil sodium. In the group as a whole, there was a significant (p less than 0.001) increase in mast cell density in tissue sections from biopsy specimens obtained during the season compared with out of season (median values, 55.0 and 15.5 cells per square millimeter, respectively). There was also a significant (p less than 0.02) increase in the density of eosinophil infiltration during the season compared with out of season (median values, 6.3 and 0 cells per square millimeter, respectively). Treatment with nedocromil sodium significantly (p less than 0.02) inhibited the accumulation of mast cells but not eosinophils. Compared with the placebo-treated group, the group treated with nedocromil demonstrated a significant (p less than 0.025) reduction in the requirements for treatment with concomitant medication (terfenadine tablets and xylometazoline/antazoline eye drops). These results indicate that natural exposure to allergen in patients with seasonal allergic rhinitis is accompanied by infiltration of mast cells and eosinophils into the nasal mucous membrane. The clinical efficacy of nedocromil sodium in this condition may be related to inhibition of infiltration by mast cells.
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PMID:Allergen-induced changes in the nasal mucous membrane in seasonal allergic rhinitis: effect of nedocromil sodium. 215 19

Amino and hydrazyno derivatives of Eupergit C were prepared by reaction of the beads with hexamethylene diamine (HMD) and adipic acid dihydrazide (ADH), respectively. Monoclonal antibodies (mAbs) against carboxypeptidase A (CPA) and horse radish peroxidase (HRP) were prepared, and those that did not inhibit the respective enzymatic activities were selected. The carbohydrate moieties of these antibodies were oxidized by reaction with sodium periodate and then coupled onto the modified beads. The oxidation and coupling reactions were optimized to achieve highly active matrix-conjugated antibodies. Thus, antibody-matrix conjugates that possessed antigen-binding activities close to the theoretical value of 2 mol antigen bound/mol immobilized antibody were obtained.
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PMID:Oriented immobilization of periodate-oxidized monoclonal antibodies on amino and hydrazide derivatives of Eupergit C. 215 62

1. Inhaled adenosine and its parent nucleotide, adenosine 5'-monophosphate (AMP) provoke bronchoconstriction in atopic and asthmatic individuals but not in normal subjects. 2. In clinical studies, histamine H1-receptor antagonists, cyclo-oxygenase inhibitors and the mast cell 'stabilising' drugs, sodium cromoglycate and nedocromil, protect against the effects of adenosine bronchoprovocation suggesting the involvement of secondary mast cell mediator release. 3. Adenosine and its analogues potentiate histamine and leukotriene release from mast cells activated by other stimuli in vitro, and may also increase net mediator release from mast cells by counteracting the inhibitory effect of circulating adrenaline. 4. Although adenosine fulfils many of the criteria required for a mediator in asthma, its importance is not fully understood, and the mechanisms by which it provokes bronchoconstriction in asthmatic subjects is far from concluded. 5. Two possibilities are that either adenosine acts directly on luminal mast cells to upregulate histamine secretion, or it acts to initiate neuronal reflexes which stimulate histamine release indirectly and possibly activate peptidergic and/or cholinergic pathways.
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PMID:Adenosine bronchoconstriction in asthma: investigations into its possible mechanism of action. 226 11


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