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

It is generally accepted that an initial step of reaginic hypersensitivity reactions is a bridging of mast cell--bound IgE antibody molecules by antigen. Since IgE molecules are firmly bound to receptors on mast cells, bridging of cell-bound IgE molecules probably brings receptor molecules into close proximity. A hypothesis was therefore presented that such a local change in membrane structure and/or possible interaction between adjacent receptor molecules may be triggering mechanisms of IgE-mediated histamine release. The hypothesis was tested by use of antibodies against "exposed portion" of receptor molecules on rat basophilic leukemia cells. It was found that antireceptor antibodies and its F(ab')2fragments induced noncytotoxic histamine release from normal rat mast cells without participation of IgE, while the monovalent Fab' fragments of the antibody failed to do so. However, sensitization of normal rat skin with the Fab' fragments followed by an intravenous injection of antirabbit IgG induced skin reactions. These findings support the concept that bridging of receptors rather than polymerization of IgE molecules is responsible for the activation of membrane-associated enzymes which in turn leads to histamine release.
 ...
PMID:A new concept of triggering mechanisms of IgE-mediated histamine release. 7 42

The gene order of the ml Moloney sarcoma virus (mlMSV) specific pP60gag (P60) was determined by direct chemical analysis of the polyprotein. P60 was cleaved with cyanogen bromide (CNBr) into eight partial and complete fragments ranging in mass from 10,000 daltons to 58,000 daltons. Peptide maps of these fragments were compared to maps of p15, p12, and three CNBr fragments of p30. The polarity of p15 and p12 in a CNBr fragment of P60 was determined by carboxypeptidase A digestion; likewise the CNBr fragments of p30 were ordered by aminopeptidase digestion. The linear arrangement of P60 CNBr fragments gave the gene order of NH2-p15-p12-p30-COOH. The m3 isolate of MSV expresses a P70 gag polyprotein. Peptide maps of 48,000-dalton CNBr fragments of m3 P70 and ml P60 were similar and suggested that both polyproteins were similar through the NH2-terminal two-thirds of p30. However, the presence of peptides unique to the 10,500-dalton COOH-terminal fragment of m1MSV p30 and not present in the p30 of either m3MSV or Moloney leukemia virus suggested that the gag gene deletion in the m1 isolate begins in the p30 reading frame.
 ...
PMID:Chemical determination of the m1 Moloney sarcoma virus pP60gag gene order: evidence for unique peptides in the carboxy terminus of the polyprotein. 21 95

The generation of slow reacting substance (SRS) from ionophore A23187-stimulated rat peritoneal mast cells was enhanced by arachidonic acid (AA). This SRS generation was inhibited by 5,8,11,14-eicosatetraynoic acid (ETYA), an acetylenic analogue of AA and an inhibitor of both fatty acid cyclooxygenase and lipoxygenase. Indomethacin, a fatty acid cyclooxgenase inhibitor, had an enhancing effect upon SRS generation. This suggests SRS generation occurred through an ETYA sensitive step--perhaps a lipoxygenase. Radiolabel from [14C]-AA was incorporated into SRS with comigration of radioactivity and bioreactivity in silicic acid and thin layer chromatographies. Upon silicic acid chromatography, the active principle was eluted in the methanol fraction. Two-dimensional thin layer chromatography revealed chromatographic separation from other known spasmogenic substances and phospholipids. Mast cell SRS was found to display physiochemical properties similar to those of rat basophilic leukemia cell SRS, namely: that mast cell SRS generation was 1) enhanced by arachidonic acid; 2) inhibited by ETYA but not by indomethacin; 3) incorporation of [14C]-AA into the active principle; and 4) similar behavior during purification in silicic acid and thin layer chromatographies.
 ...
PMID:Slow reacting substance (SRS) from ionophore A23187-stimulated peritoneal mast cells of the normal rat. II. Evidence for a precursor role of arachidonic acid and further purification. 37 31

Inhibition of mediator release from mast cells and basophils by diisopropylfluorophosphate (DFP) and other organophosphorus compounds known to inhibit serine esterases has in the past led to the hypothesis that immunologic triggering of these cells involves an activatable serine esterase. In this study we have shown that two nonphosphorylating or poorly phosphorylating structural analogs of two potent phosphorylators inhibit release of incorporated serotonin from cultured rat basophil leukemia cells. We conclude that, by itself, inhibition of immunologic mast cell triggering by phosphorylating organophosphorus compounds can no longer be considered evidence for involvement of an activatable serine esterase in mast cell triggering.
 ...
PMID:IgE mediated triggering of rat basophil leukemia cells: lack of evidence for serine esterase activation. 44 21

Human mast cells and basophil granulocytes can be easily recognized in normal tissues by light microscopy. In one mast cell and one basophilic leukemic case considered in this study, mast cells and basophils were morphologically quite similar and could not therefore be clearly defined merely by their morphological features. Both types of cells showed round nuclei and deep purple granules. The diagnosis of mast cell leukemia or basophilic leukemia was made on the basis of different cytochemical patterns. In the case of mast cell leukemia, peroxidase and PAS stains were negative, while chloroesterase was strongly positive; in the case of basophilic leukemia, peroxidase and PAS stains were positive, while chloroesterase reaction showed a peculiar pattern. Toluidine blue metachromasia and astra blue positivity were present in the cells of both cases.
 ...
PMID:Mast cell leukemia and acute basophilic leukemia. Cytochemical studies. 74 30

Recent studies on the receptor for IgE on rat mast cells and rat basophilic leukemia cells have established that this receptor has a molecular weight of about 60,000 daltons and is, at least in part, a protein. However, so far no antisera, monospecific for this receptor, are available. Only antisera to mast cells have been described. Such antisera are capable of releasing histamine from mast cells, but only in the presence of complement. In most instances such antisera were not specific for mast cells only, but in some cases they were rendered specific by absorption with lymph node cells or liver cells. One report demonstrates that such an absorbed antiserum was capable of inhibiting the binding of IgE to mast cells. Moreover, it precipitated several mast cell surface components. One of these possibly was the receptor for IgE.
 ...
PMID:Antisera to mast cells and the receptor for IgE. 78 66

Aggregation of the high affinity receptor for IgE (Fc epsilon RI) on the surface of mast cells results in the rapid hydrolysis of membrane inositol phospholipids by phospholipase C (PLC). Although at least seven isoenzymes of PLC have been characterized in different mammalian cells, the isoenzyme involved in Fc epsilon RI-mediated signal transduction and the mechanism of its activation have not been demonstrated. We now report that PLC-gamma 1 is translocated to the membrane of mast cells after aggregation of Fc epsilon RI. Activation of rat basophilic leukemia cells, a rat mast cell line, with oligomeric IgE resulted in an increase in PLC activity in washed membrane preparations in a cell free assay containing exogenous [3H]phosphatidylinositol (PI). The increase in PLC activity has the same dose-response to oligomeric IgE as receptor mediated hydrolysis of inositol lipids (PI hydrolysis) in intact cells. Analysis by Western blot probed with anti-PLC-gamma 1 antibody revealed that there is a three- to fourfold increase in PLC-gamma 1 in membranes from activated cells. The increase in PLC activity is augmented a further 20% by the addition of orthovanadate to the incubation medium suggesting that a tyrosine phosphatase is involved in the down-regulation of this phenomenon. These findings demonstrate translocation of PLC-gamma 1 to the membrane following activation of a receptor which does not contain intrinsic tyrosine kinase activity. Activation of PLC-gamma 1 by this pathway may account for Fc epsilon RI-mediated PI hydrolysis.
 ...
PMID:Phospholipase C-gamma 1 is translocated to the membrane of rat basophilic leukemia cells in response to aggregation of IgE receptors. 131 4

The concept of mast cell heterogeneity has been studied extensively. Recently developed techniques to enzymatically disperse skin mast cells from human skin have shown that skin mast cells are somehow different from those of other organs such as lung and intestine. In this report, we have isolated and partially purified human skin mast cells from human neonatal foreskins by collagenase and hyaluronidase digestion. These mast cells are morphologically intact by histological, immunohistochemical and electron microscopic criteria. These human skin mast cells secrete histamine significantly (max. net histamine release, 20-30%) in a dose-related, temperature- and time-dependent fashion following stimulation with purified human C5a and C3a (over the ranges of 5 x 10(-8) M to 10(-7) M and 3 x 10(-7) M to 6 x 10(-6) M, respectively). On the other hand, interactions between human skin mast cells and other leukocytes have long been suspected of playing a very important role in cutaneous inflammation. Recently, a human neutrophil-derived histamine-releasing activity termed HRA-N was partially purified. HRA-N has been shown to cause human and rat basophil leukemia cells to degranulate. This study was also undertaken to assess the ability of HRA-N to directly induce histamine release from isolated human skin mast cells. HRA-N causes dose- and time-dependent histamine release as do human anaphylatoxins. These results suggest that HRA-N may lead to a better comprehension of allergic and inflammatory reactions and their modulation in the skin.
 ...
PMID:The effect of human anaphylatoxins and neutrophils on histamine release from isolated human skin mast cells. 137 10

The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of activities with respect to IgE receptor (Fc epsilon RI)-mediated exocytosis from mast cells and T cell receptor-mediated transcription of IL-2. These findings suggest a common step in receptor-mediated signal transduction leading to exocytosis and transcription and imply that immunosuppressive drugs target specific signal transduction pathways, rather than specific cell types. This hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is prevented in a competitive manner by FK506, a structural analogue of rapamycin. Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also inhibited, at doses comparable to those shown previously to inhibit IL-2-dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast, proliferation of A-431 cells, a epidermoid cell line, was not affected by rapamycin. DNA histograms indicate that complexes formed between the rapamycin-FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit proliferative signals emanating from IL-3 receptors, resulting in growth arrest of cytokine-dependent, hematopoietic cells.
 ...
PMID:The effect of the immunophilin ligands rapamycin and FK506 on proliferation of mast cells and other hematopoietic cell lines. 138 15

In RBL-2H3 rat basophilic leukemia cells, Ca2+ influx and secretion are activated by antigens that crosslink IgE-receptor complexes and by the Ca2+ ionophore, ionomycin. Here we report that antigen-stimulated Ca2+ influx and secretion are impaired and ionomycin-induced responses are strongly inhibited following the removal of HCO3- from the medium. These results raised the possibility that HCO3(-)-dependent pH regulation mechanisms play a role in the cascade of events leading to mast cell activation. To test this hypothesis, intracellular pH (pHi) was measured by ratio imaging microscopy in individual RBL-2H3 cells labeled with 2',7'-bis-(2-carboxyethyl)-5-(6) carboxyfluorescein (BCECF). In unstimulated cells, it was found that basal pHi in the presence of HCO3- is 7.26, significantly greater than pHi in its absence, 7.09 (P less than 10(-6]. These results, as well as evidence that pHi increases rapidly when HCO3- is added to cells initially incubated in HCO3(-)-free medium, indicate that unstimulated cells use a HCO3(-)-dependent mechanism to maintain cytoplasmic pH. Further analyses comparing unstimulated with stimulated cells showed that antigen causes a small transient acidification in medium containing HCO3- and a larger sustained acidification in HCO3(-)-depleted medium. Ionomycin is a more potent acidifying agent, stimulating a sustained acidification in complete medium and causing further acidification in HCO3(-)-free medium. These results support the hypothesis that the inhibition of antigen- and ionomycin-induced 45Ca2+ influx and secretion in cells incubated in HCO3(-)-free medium is at least partially due to the inactivation of HCO3(-)-dependent mechanisms required to maintain pH in unstimulated cells and to permit pH recovery from stimulus-induced acidification.
 ...
PMID:Importance of bicarbonate ion for intracellular pH regulation in antigen- and ionomycin-stimulated RBL-2H3 mast cells. 154 61


1 2 3 4 5 6 7 8 9 10 Next >>