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)

In washed human platelets and in HL60 granulocytes phorbol myristate acetate (PMA, 1-2000nM) synergised with threshold concentrations of secretogogues to induce a sustained maximum secretory response. Likewise, superoxide production from HL60 cells maintained a maximal response at PMA concentrations between 30-300nM. At concentrations up to 10nM PMA also augmented calcium ionophore, A23187, stimulated histamine release from rat peritoneal mast cells. However, in the mast cell PMA concentrations above 10nM reduced maximum histamine release in a dose-dependent manner.
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PMID:Stimulation and inhibition of secretion by phorbol myristate acetate in different cell types. 258 May 26

Mast cell heterogeneity has been described on the basis of differential staining reactions, light microscopic morphology, anatomic location, degranulation after polyamines, biochemical contents, growth requirements, and reactions to lymphokines. We have demonstrated typical "connective-tissue mast cells" by using anatomic criteria, histological staining reactions, electron microscopy, and reaction to compound 48/80 in the guinea pig conjunctiva, eyelid skin, and ileum. A second, much larger population of cells in the ileal mucosa and the conjunctiva, and rarely in the eyelid skin stained reddish-blue with acid toluidine blue in tissue fixed in ethanol-acetate-lead subacetate (BLA) and with alkaline Giemsa in formaldehyde-fixed tissue, did not stain with ethanolic or acid toluidine blue in formaldehyde-fixed tissue or with alkaline Giemsa in BLA-fixed tissue, and did not degranulate after 48/80 treatment. These are features of the rat intestinal "mucosal mast cells"; however, ultrastructural and light microscopic studies with the orcein Giemsa stain demonstrated these cells in the guinea pig to be eosinophils. Tissue culture, biochemical, and immunological studies indicate the existence of a second type of mast cell (bone-marrow-derived mast cell), ultrastructurally almost indistinguishable from the connective tissue mast cell. Our studies demonstrate only one mast cell type in the guinea pig and support the contention that other forms of mast cells are immature forms or variants of the connective-tissue mast cell.
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PMID:Eosinophils and mast cell homogeneity of the guinea pig eyelid skin, conjunctiva, and ileum. 258 20

The tongue, pinna and dorsal skin of adult male C-1 mice were removed at 03.00, 06.00, 09.00, 12.00, 15.00, 18.00, 21.00 and 24.00 h, fixed in basic lead acetate and stained with Alcian blue-safranin or 0.5% toluidine blue. The mast cell numbers of these regions were counted and analyzed statistically by analysis of variance. It was found that there were circadian variations in the mast cell number in the tongue, pinna and dorsal skin. The difference between the minimum and maximum of circadian variation in mast cell number in all three regions was highly significant (p less than 0.01). Furthermore, the time points of the maximum and minimum of mast cell number varied between the different regions. The time point of the minimum in the tongue and pinna was at 06.00 h, whereas it was at 09.00 h in the dorsal skin. The time point of the maximum in the tongue and dorsal skin was at 21.00 h, but in the pinna it was at 18.00 h.
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PMID:Quantitative study of circadian variations in mast cell number in different regions of the mouse. 260 35

Biochemical information regarding the mechanism of amide bond hydrolysis offers insight into the possible chemical groups in the enzyme active site responsible for hydrolysis. Assuming that these groups have a relatively fixed geometry in accord with their functional role, then their three-dimensional position in space can be determined if sufficient structural diversity exists within the data set of compounds with known affinities. Each compound which binds can be augmented by additional chemical groups to represent the receptor's functional groups. For each compound, the set of geometrical arrangements of these groups which would show optimal binding to the compound can be determined by systematic search. A common geometric arrangement representing the active site geometry should be present for each compound. In studies of the binding of mechanism-based inhibitors of chymotrypsin, Naruto et al. (1985) showed some movement of active site residues to accommodate different ligands. Nevertheless, this procedure found a unique active site geometry for ACE which compared favorably with that of carboxypeptidase A, an enzyme of analogous function.
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PMID:Mechanism-based analysis of enzyme inhibitors of amide bond hydrolysis. 272 59

The interleukin-2-dependent mouse natural killer (NK) cell line NKB61A2 concomitantly exhibits NK and natural cytotoxic (NC) activities. This was determined by the cells' ability to lyse both the NK-sensitive YAC-1 lymphoma and the NC-sensitive WEHI-164 fibrosarcoma cell lines in a 4- and 18-hour 51Cr release assay, respectively. Cell-free supernatant from NKB61A2 cells grown in culture for 48 h had substantial lytic activity against WEHI-164. The mouse mast cell line PT18-A17 and the rat basophilic leukemia cell line RBL-2H3, which both express NC activity, also produced a soluble factor during culture which lysed WEHI-164 cells. This activity was increased in the basophilic/mast cells by crossbridging the surface IgE receptors. Similar results were obtained by triggering the basophilic NC cells with the calcium ionophore ionomycin and the tumor promoter phorbol-12-myristate-13-acetate (PMA). Such triggering of NKB61A2 cells, however, did not significantly increase their NC activity. Interestingly, both ionomycin and PMA had an inhibitory effect on the NK activity of NKB61A2. Recently it has been found that tumor necrosis factor (TNF) is a major mediator of NC activity. To determine if the soluble factor responsible for the NC activity of the NK clone was related to TNF, a rabbit polyclonal antiserum to mouse TNF was tested against the cell-free culture medium of NKB61A2, PT18-A17, RBL-2H3 and murine recombinant TNF (Mu-rTNF). The lytic activity of the culture medium from all these cells and the Mu-rTNF control was abrogated by this antibody. These data suggest that the murine cell line NKB61A2 has both NK and NC activities and that the NC activity is due to a factor immunologically similar to TNF. In addition, the enhancement of NC activity in the NK cell line is apparently under control by a separate pathway, different from that in the basophilic cells.
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PMID:Natural cytotoxic activity in a cloned natural killer cell line is mediated by tumor necrosis factor. 276 50

Colony-stimulating factors (CSFs) produced by two simian virus 40(SV40) transformed macrophage cell lines (BAM1 and BAM3), and three hybrids (HM3-11, HM3-12, and HM3-14) derived from fusion between BAM3 and a Chinese hamster cell line (hs222-16) were examined. HM3-11 and HM3-14 produce two molecular species of CSF, which are not found in the conditioned media from cultures of BAM1 and BAM3 or lipopolysaccharide (LPS), phorbolmyristate-acetate (PMA), and zymosan-stimulated BAM3. HM3-12, which is classified into another group in terms of CSF secretion, does not produce these two CSFs. On the basis of various criteria, one of these CSF species (peak 1-CSF) was characterized as a macrophage-colony-stimulating factor (M-CSF). The other CSF (peak 2-CSF) induced a group of bone marrow cells in granulocytes and macrophages as well as growth of a mast cell line, IC2. This CSF has an apparent molecular weight of 18,000, estimated by SDS-polyacrylamide gel electrophoresis. Unlike interleukin 3 (IL3) from WEHI-3 cells, the growth factor activity of peak 2-CSF binds to DEAE-Sephacel. Thus, peak 2-CSF is similar to a granulocyte-macrophage colony-stimulating factor (GM-CSF) rather than to IL3. The anti L cell CSF serum does not inhibit the CSF activity in Chinese hamster fibroblast conditioned medium, and the IC2 cells do not respond to Chinese hamster lung conditioned medium (CHLCM), suggesting that peak 1- and peak 2-CSF are of mouse origin.
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PMID:Properties of colony-stimulating factors produced by macrophage cell lines and hybrid cells. 302 9

Cutaneous mastocytomas were observed in female CD-1 mice following long-term application of three types of cigarette smoke condensate suspensions ("tars") from different cigarettes or of 7,12-dimethylbenz(a)anthracene (DMBA) and tetradecanoylphorbol-acetate (TPA) or tars. These mastocytomas were always accompanied by diffuse dermal mast cell infiltration (DDMI). These results indicate that mastocytomas were induced by agents present in the cigarette smoke condensate of DMBA plus TPA.
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PMID:Mastocytoma induced by cigarette smoke particulates: "cigarette tar". 310 73

Inflammatory reactions induced by TPA (12-O-tetradecanoylphorbol 13-acetate)-type tumor promoters, including TPA, teleocidin and aplysiatoxin, and chemical mediators responsible for such inflammatory reactions were analyzed. The tumor promoter dissolved in a 0.8% sodium carboxymethyl cellulose solution was injected into a subcutaneous air pouch preformed on the dorsum of rats. Within 30 min after the injection, vascular permeability as measured by the leakage of labeled albumin into the pouch fluid was increased, with a concomitant increase in histamine level. This increase in vascular permeability was inhibited by a histamine antagonist, pyrilamine, and a serotonin antagonist, methysergide. Vascular permeability at 4 h was not inhibited by pyrilamine or methysergide but was inhibited by a cyclooxygenase inhibitor, indomethacin, with a parallel decrease in the prostaglandin E2 level in the pouch fluid. These results suggest that the TPA-type tumor promoters induce inflammation by the mechanism of mast cell degranulation within a short period, this being followed by the stimulation of arachidonic acid metabolism. The mechanism of the in vivo effect of the TPA-type tumor promoters is discussed and compared with in vitro effects that we have previously reported.
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PMID:Analysis of tumor-promoter-induced inflammation in rats: participation of histamine and prostaglandin E2. 311 92

The binding of L- and D-phenylalanine and carboxylate inhibitors to cobalt(II)-substituted carboxypeptidase A, Co(II)CPD (E), in the presence and absence of pseudohalogens (X = N3-, NCO-, and NCS-) has been studied by 1H NMR spectroscopy. This technique monitors the proton signals of histidine residues bound to cobalt(II) and is therefore sensitive to the interactions of inhibitors that perturb the coordination sphere of the metal. Enzyme-inhibitor complexes, E.I, E.I2, and E.I.X, each with characteristic NMR features, have been identified. Thus, for example, L-Phe binds close to the metal ion to form a 1:1 complex, whereas D-Phe binds stepwise, first to a nonmetal site and then to the metal ion to form a 2:1 complex. Both acetate and phenylacetate also form 2:1 adducts stepwise with the enzyme, but beta-phenylpropionate gives a 2:1 complex without any detectable 1:1 intermediate. N3-, NCO-, and NCS- generate E.I.X ternary complexes directly with Co(II)CPD.L-Phe and indirectly with the D-Phe and carboxylate inhibitor 2:1 complexes by displacing the second moiety from its metal binding site. The NMR data suggest that when the carboxylate group of a substrate or inhibitor binds at the active site, a conformational change occurs that allows a second ligand molecule to bind to the metal ion, altering its coordination sphere and thereby attenuating the bidentate behavior of Glu-72. The 1H NMR signals also reflect alterations in the histidine interactions with the metal upon inhibitor binding. Isotropic shifts in the signals for the C-4 (c) and N protons (a) of one of the histidine ligands are readily observed in all of these complexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:1H NMR spectroscopic characterization of binary and ternary complexes of cobalt(II) carboxypeptidase A with inhibitors. 324 89

Cutaneous mast cell degranulation in rats results in tissue inflammation, and this species has therefore provided a useful model to study the pathogenesis of late phase reactions (LPRs). The mast cell dependency of LPRs has been confirmed by the demonstration that isolated rat mast cell granules (MCGs), when injected intradermally into rat skin, induce patterns of tissue inflammation similar to those seen after skin testing with anti-IgE antibody. Rat LPRs are neutrophil dependent, and, further, MCG-derived inflammatory factors can chemically attract rat neutrophils in vitro. To further study the relationships among MCGs, tissue inflammation, and neutrophil function, luminol-dependent chemiluminescence (CL) responses of rat peritoneal-elicited neutrophils in response to opsonized zymosan and phorbol myristate acetate (PMA) in the presence and absence of MCGs were analyzed. When MCGs (1.0, 10, and 100 micrograms/ml) alone were added to neutrophil suspensions, a rapid concentration-dependent increase in baseline CL responses was observed; these increases (maximum of sixfold) were modest, varied with cell concentrations, and followed different time courses compared with those seen after addition of preopsonized zymosan (0.5 mg/ml) (50-fold increases that peaked in 4 to 8 minutes). However, if neutrophils were preincubated (15 minutes) in the presence of MCGs, the CL response to opsonized zymosan (1.25 mg/ml) was significantly and synergistically enhanced compared with the response seen with MCGs alone. Similar but less pronounced effects were also noted after cell activation with PMA (2.5 and 25 ng/ml). To determine which component of the MCG was responsible for this enhancing activity, additional experiments were performed. Enhancement was still observed, albeit less intense, if MCGs were prepared membrane free and washed free of readily dissociable mediators such as histamine. Histamine (10(-6) and 10(-5) mol/L) had no enhancing effect nor did preparations of MCG membranes. MCG solubilization (3 mol/L NH4HCO3) revealed that the enhancing activity resided completely in the high molecular weight (greater than 10,000 daltons) fraction. Heat treatment of the granules and sodium azide preincubation completely abolished the enhancing effect. Exogenous horseradish peroxidase, at peroxidase activity levels contained within the MCGs (1 x 10(-4) to 10(-2) U/ml), reproduced the enhancing effect. After opsonized zymosan activation, neutrophils generated less H2O2 and superoxide anion in the presence of MCGs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Mast cell granule enhancement of neutrophil chemiluminescence responses. 334 48


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