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)

beta-Hexosaminidase, beta-glucuronidase, arylsulfatase, and tryptase were each released along with histamine from dispersed purified human lung mast cells of 40 to 80% purity by rabbit IgG anti-human IgE. The net per cent release ratio of each enzyme to histamine was determined over all doses of antibody employed to activate the mast cells and over all time points after activation, and indicated the per cent of each enzyme stored in secretory granules along with histamine. By multiplying the net per cent release ratio of each enzyme to histamine by total enzyme content in a preparation of 10(6) mast cells, values for secretory granule content per 10(6) mast cells were found to be 3.8 U for beta-hexosaminidase, 0.03 U for beta-glucuronidase, 0.03 U for arylsulfatase, and 0.9 U for tryptase. Subtype analysis of beta-hexosaminidase by diethylaminoethyl- (DEAE) cellulose chromatography revealed that the B isomer predominates in human mast cell secretory granules, whereas the A isomer predominates in secretory granules of the rat mast cell. Tryptase, the predominant neutral protease of the human mast cell secretory granule, has a m.w. of 130,000 by gel filtration chromatography, whereas the major neutral protease of the rat mast cell is chymotryptic and of 25,000 m.w. The presence of acid hydrolases, a tryptase, and histamine in human mast cell secretory granules suggests that the activated mast cell plays a direct role in the production of acute and subacute inflammation.
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PMID:Acid hydrolases and tryptase from secretory granules of dispersed human lung mast cells. 700 36

Padawer has proposed that rat mast cells in the peritoneal cavity have an extended lifespan and under normal conditions exhibit little turnover of their secretory granules. We have examined several constituents of the granules as part of a study of the structure and function of these organelles. The previously described increase in volume of mast cells with age of the rats from which the cells are obtained is associated with an increase in the quantity of histamine, heparin, beta-glucuronidase and mast cell protease. While the former 3 granule components increase in parallel with mast cell volume, the increase in protease between 3- and 6-month-old rats is in excess of cell volume and the other 3 granule component. Granules from rats 1 month or less in age tend to be more difficult to isolate with their surrounding membranes intact.
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PMID:Effect of age on mast cell granules. 723 98

Norathyriol, a xanthone aglycon isolated from Tripterospermum lanceolatum, was demonstrated to reduce the plasma leakage elicited by the passive cutaneous anaphylactic reaction in normal as well as in adrenalectomized mice. Capsaicin pretreatment greatly suppressed the local edema caused by antidromic stimulation of the saphenous nerve. The plasma exudation of neurogenic inflammation was also reduced in mice treated with norathyriol, diphenhydramine and methysergide, but not with indomethacin. Norathyriol, cyproheptadine and diphenhydramine combined with methysergide suppressed the ear edema caused by injection of compound 48/80, bradykinin and substance P into the ear. However, indomethacin did not affect this phlogist-induced edema response. Histamine- and serotonin-induced plasma exudation in ear edema was also reduced by norathyriol. In isolated rat peritoneal mast cell preparations, norathyriol produced a dose-dependent inhibition of histamine and beta-glucuronidase release from mast cells challenged by compound 48/80, bradykinin and substance P. In compound 48/80-pretreated mice, norathyriol at higher concentrations suppressed the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine combined with methysergide did. These data indicate that the inhibitory effect of norathyriol on local edema is not due to the release of steroid hormones from the adrenal gland, but is probably partly due to suppression of mast cell degranulation and hence reduce the release of chemical mediators which increase vascular permeability, and partly, at least in higher doses, due to protection of the vasculature from challenge by various mediators.
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PMID:Inhibitory effect of norathyriol, a xanthone from Tripterospermum lanceolatum, on cutaneous plasma extravasation. 751 Nov 7

Acetylshikonin, a naphthoquinone isolated from the Chinese herb medicine, tzu ts'ao, was demonstrated to inhibit the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. Liver glycogen content was increased in adrenalectomized mice pretreated with dexamethasone, but not with acetylshikonin. Like diphenhydramine, methysergide and isoproterenol, acetylshikonin reduced the plasma exudation evoked in dorsal hind-paw skin by antidromic stimulation of the saphenous nerve, and in passive cutaneous anaphylactic reaction, bradykinin-, substance P-, compound 48/80-, histamine- and serotonin-induced ear edema. Indomethacin was ineffective in these respects. Bradykinin- and substance P-induced plasma exudation were also significantly reduced when [Thi5,8,D-Phe7]bradykinin and [D-Pro2,D-Trp7,9]substance P were coinjected with bradykinin and substance P, respectively. In isolated rat peritoneal mast cell preparation, acetylshikonin produced a concentration-dependent inhibition of histamine and beta-glucuronidase release from mast cells challenged by compound 48/80. In compound 48/80-pretreated mice, acetylshikonin and isoproterenol produced significantly more inhibitory effect on bradykinin- and substance P-induced plasma exudation than did diphenhydramine in combination with methysergide. Pretreatment with diphenhydramine/methysergide in compound 48/80-pretreated mice significantly further reduced the bradykinin- and substance P-induced plasma exudation if [Thi5,8,D-Phe7]bradykinin and [D-Pro2,D-Trp7,9]substance P were coinjected with bradykinin or substance P, respectively. The results suggest that the inhibitory effect of acetylshikonin on the edematous response is due neither to the release of steroid hormones from the adrenal gland nor to the glucocorticoid activity, but probably partly to the suppression of mast cell degranulation and partly to protection of the vasculature from mediator challenge.
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PMID:Inhibition of hind-paw edema and cutaneous vascular plasma extravasation in mice by acetylshikonin. 753 60

Polymyxin B-induced hind-paw edema was suppressed by abruquinone A, an isoflavanquinone isolated from Abrus precatorius, in normal as well in adrenalectomized mice. Unlike dexamethasone, abruquinone A did not increase the liver glycogen content in fasting adrenalectomized mice. The volume of exuded plasma was significantly reduced by abruquinone A in neurogenic inflammation, passive cutaneous anaphylactic reaction and compound 48/80-induced ear edema. Histamine-, serotonin-, bradykinin- and substance P-induced plasma extravasation in ear edema was also suppressed by abruquinone A. Abruquinone A, like isoproterenol, significantly reduced the bradykinin- and substance P-induced plasma extravasation in normal as well as in compound 48/80-pretreated mice. In addition, abruquinone A suppressed the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine/methysergide did. In the in vitro experiments, abruquinone A suppressed the compound 48/80-induced histamine and beta-glucuronidase released from isolated rat peritoneal mast cell preparations. These results suggest that the anti-inflammatory effect of abruquinone A is mediated partly via the suppression of the release of chemical mediators from mast cells and partly via the prevention of vascular permeability changes caused by mediators. The glucocorticoid activity and the release of glucocorticoid hormones from the adrenal gland are probably not involved.
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PMID:Inhibition of plasma extravasation by abruquinone A, a natural isoflavanquinone isolated from Abrus precatorius. 753 81

Eighteen synthetic xanthone derivatives were tested for their inhibitory effects on the activation of mast cells and neutrophils. 1,3- and 3,5-Dihydroxyxanthone showed strong inhibitory effects on the release of beta-glucuronidase and histamine from rat peritoneal mast cells stimulated with compound 48/80. 1,6-Dihydroxyxanthone and 1,3,8-trihydroxyxanthone showed strong inhibitory effects on the release of beta-glucuronidase, and beta-glucuronidase and lysozyme, respectively, from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP). 1,3- and 1,6-Dihydroxyxanthone, 1,3,7-trihydroxyxanthone, and 1,3,5,6-, 2,3,6,7-, and 3,4,5,6-tetrahydroxyxanthone showed potent inhibitory effects on superoxide formation of rat neutrophils stimulated with fMLP. 1,6- and 3,5-Dihydroxyxanthone showed remarkable inhibitory effects on hind-paw oedema induced by polymyxin B in normal as well as in adrenalectomized mice. These data indicated that the anti-inflammatory effect of these compounds is mediated through the suppression of chemical mediators released from mast cell and neutrophil degranulation.
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PMID:Synthesis and anti-inflammatory effects of xanthone derivatives. 879 82

Neutrophils contain various antibacterial polypeptides and proteins in the granules. Defensins have been known as the major antimicrobial granular components. Recently, we have purified a novel cationic antibacterial polypeptide of 11 kDa (CAP11) from guinea pig neutrophil granules. In this study, we have examined the extracellular release and biological activity of CAP11, and compared with defensins. CAP11 was extracellularly released from neutrophils by N-formyl Met-Leu-Phe, phorbol 12-myristate 13-acetate, accompanied by the release of lysozyme, a specific and azurophil granule component, without release of beta-glucuronidase, an azurophil granule component, whereas defensins were released by phagocytosis, accompanied by the release of beta-glucuronidase, suggesting that the localization of CAP11 and defensins is different among neutrophil granules. Defensins increased neutrophil adhesion, and inhibited phagocytosis of opsonized zymosan particles and phagocytosis-associated superoxide anion generation. In contrast, CAP11 did not affect these neutrophil functions. Both CAP11 and defensins possessed the histamine-releasing activities for mast cells, but CAP11 was 10-fold less potent than defensins. CAP11 and defensins showed the antibacterial activities against both Escherichia coli and Staphylococcus aureus. However, the antibacterial activity of defensins was completely lost in the presence of physiological concentration of NaCl (0.15 M), although CAP11 retained the antibacterial activity even in the presence of NaCl. Furthermore, CAP11 exhibited the 10-fold more potent antiretroviral activity than defensins against Moloney murine leukemia viruses. Together these observations indicate that when released from neutrophils, CAP11 likely functions as an antimicrobial molecule in the extracellular milieu, whereas defensins may participate in the modulation of neutrophil function and mast cell histamine release.
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PMID:Comparative studies on the extracellular release and biological activity of guinea pig neutrophil cationic antibacterial polypeptide of 11 kDa (CAP11) and defensins. 908 Jun 67

Mast cells, neutrophils, and macrophages are important inflammatory cells that have been implicated in the pathogenesis of acute and chronic inflammatory diseases. To explore a novel antiinflammatory agent, we have synthesized two types of acridines, 9-anilinoacridine and 9-phenoxyacridine derivatives, for evaluation on the grounds that acridine is a versatile heterocycle possessing a wide variety of biological properties. The title compounds were synthesized by reaction of 9-chloroacridine with appropriate Ar-NH(2) and Ar-OH, and their antiinflammatory activities on inhibitory effects on the activation of mast cells, neutrophils, and macrophages were studied. Three acridine derivatives 4, 10, and 11 were proved to be more potent than the reference inhibitor mepacrine for the inhibition of rat peritoneal mast cell degranulation with similar IC(50) values (16-21 microM). Compound 3 also showed potent inhibitory activity (IC(50) = 8.2 and 4.4 microM, respectively) for the secretion of lysosomal enzyme and beta-glucuronidase from neutrophils. Moreover, compounds 5 and 9 were shown to be efficacious inhibitors of TNF-alpha production in macrophage-like cell lines RAW 264.7. Compounds 2 and 12 were the potent inhibitors of TNF-alpha production in murine microglial cell lines N9. To further explore the cytotoxic properties of these acridine derivatives, (E)-12 was selected for NCI's in vitro disease-oriented tumor cells screen. The results indicated that this compound had no significant cytotoxicity with a mean GI(50) of 58.0 microM. These results indicated that the antiinflammatory effects of acridine derivatives were mediated, at least in part, through the suppression of chemical mediators released from mast cells, neutrophils, and macrophages and that these compounds have the potential to be novel antiinflammatory agents with no significant cytotoxicity.
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PMID:Synthesis and antiinflammatory evaluation of 9-anilinoacridine and 9-phenoxyacridine derivatives. 1236 95

Mast cells, neutrophils and macrophages are important inflammatory cells that have been implicated in the pathogenesis of acute and chronic inflammatory diseases. To explore a novel anti-inflammatory agent, we have synthesized certain 9-phenoxyacridine and 4-phenoxyfuro[2,3-b]quinoline derivatives and evaluated their anti-inflammatory activities. The title compounds were synthesized by reaction of either 9-chloroacridine or 3,4-dichlorofuro[2,3-b]quinoline with appropriate Ar-OH and their anti-inflammatory activities were studied on inhibitory effects on the activation of mast cells, neutrophils and macrophages. Four 9-(4-formylphenoxy)acridine derivatives 2b-2e were proved to be more potent than the reference inhibitor, mepacrine for the inhibition of rat peritoneal mast cell degranulation with IC(50) values of 6.1, 5.9, 13.5, and 4.7 microM, respectively. Compounds 2c, 3b, 3c, and 5a also showed potent inhibitory activity (IC(50)=4.3-18.3 microM) for the secretion of lysosomal enzyme and beta-glucuronidase from neutrophils. In addition, 2d, 3a, and 4 inhibited TNF-alpha formation from the N9 cells (the brain resident macrophages) with IC(50) vales less then 10 microM. These results indicated that acridine derivatives exhibited more potent anti-inflammatory activities than their respective furo[2,3-b]quinoline counterparts (4 vs 9; 5a vs 10a; 5b vs 10b).
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PMID:Synthesis and anti-inflammatory evaluation of 9-phenoxyacridine and 4-phenoxyfuro[2,3-b]quinoline derivatives. Part 2. 1292 52

Mast cells, neutrophils and macrophages are important inflammatory cells that have been implicated in the pathogenesis of acute and chronic inflammatory diseases. To explore a novel anti-inflammatory agent, we have synthesized certain 4-anilinofuro[2,3-b]quinoline and 4-phenoxyfuro[2,3-b]quinoline derivatives and evaluated their anti-inflammatory activities by reaction of 3,4-dichlorofuro[2,3-b]quinoline with appropriate Ar-NH(2) or Ar-OH. Compounds 6a and 15 were proved to be more potent than the reference inhibitor, mepacrine for the inhibition of rat peritoneal mast cell degranulation with IC(50) values of 6.5 and 16.4 microM, respectively. Compounds 2b, 6a, 10, and 15 also showed potent inhibitory activity (IC(50)=7.2-29.4 microM) for the secretion of lysosomal enzyme and beta-glucuronidase from neutrophils. These results also indicated that oxime derivatives are more potent than the respective ketone precursors (6a> or =2a; 7a> or =3), and the substituent such as Me at the oxime decreased inhibitory activity (6a> or =6b; 7a> or =7b). Among these derivatives, compound 6a showed the most potent activity with IC(50) values of 6.5-11.6 microM for the inhibition of mast cell degranulation and neutrophil degranulation.
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PMID:Synthesis and anti-inflammatory evaluation of 4-anilinofuro[2,3-b]quinoline and 4-phenoxyfuro[2,3-b]quinoline derivatives. Part 3. 1472 57


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