Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the signal transduction of serotonin secretion by stimulation with DNP-Ascaris antigen or ionomycin in rat basophilic leukemia cells (RBL-2H3). The modes of action of antigen and ionomycin for serotonin secretion were shown to be similar. The treatment of cells with antigen resulted in increased tyrosine phosphorylation of 105 and 72 KDa proteins, in particular, the tyrosine phosphorylation of 72 KDa protein seemed to correlate with serotonin secretion. Furthermore, we observed that antigen stimulation caused a marked increase in inositol polyphosphates production, which derived from the tyrosine phosphorylation of phospholipase C-gamma in RBL-2H3 cells. On the other hand, treatment with ionomycin also resulted in an increase in tyrosine phosphorylation of 72 KDa protein, but did not induce inositol polyphosphates production. These results suggested that the activation of tyrosine kinase may be related to serotonin secretion, and that intracellular Ca2+ increase may also play an important role in this activation.
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PMID:[The signal transduction of serotonin secretion involves protein tyrosine phosphorylation in rat basophilic leukemia cells]. 129 Apr 15

The aggregation of IgE anchored to high-affinity Fc epsilon receptors on rat basophilic leukemia (RBL) cells by multivalent antigens initiates transmembrane signaling and ultimately cellular degranulation. Previous studies have shown that the rate of dissociation of bivalent and multivalent DNP ligands from RBL cells sensitized with anti-DNP IgE decreases with increasing ligand incubation times. One mechanism proposed for this effect is that when IgE molecules are aggregated, a conformational change occurs that results in an increase in the intrinsic affinity of IgE for antigen. This possibility was tested by measuring the equilibrium constant for the binding of monovalent DNP-lysine to anti-DNP IgE under two conditions, where the cell-bound IgE is dispersed and where it has been aggregated into visible patches on the cell surface using anti-IgE and a secondary antibody. No difference in the equilibrium constant in these two cases was observed. We also measured the rate of dissociation of a monovalent ligand from cell surface IgE under these two conditions. Whereas the affinity for monovalent ligand is not altered by IgE aggregation, we observe that the rate of ligand dissociation from IgE in clusters is slower than the rate of ligand dissociation from unaggregated IgE. These results are discussed in terms of recent theoretical developments concerning effects of receptor density on ligand binding to cell surfaces.
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PMID:Aggregation of IgE-receptor complexes on rat basophilic leukemia cells does not change the intrinsic affinity but can alter the kinetics of the ligand-IgE interaction. 153 98

Mast cells and basophils have been known to play a central role in allergic inflammation through the release of chemical mediators by cross-linkage of IgE receptors. The IgE receptor triggering and calcium ionophore A23187 have also been shown to induce gene expression and production of tumor necrosis factor (TNF) by rat basophilic leukemia cells. In the present study, we examined whether IgE receptor triggering could induce gene expression and production of TNF in rat lung tissue. The lung tissue released not only histamine but also cytotoxic activity on L929 cells 2 and 4 h after incubation with dinitrophenyl conjugated to ovalbumin (DNP-OVA) following passive sensitization with anti-DNP monoclonal rat IgE antibody, whereas neither DNP-OVA nor anti-DNP IgE antibody could induce the cytotoxic activity when used solely. Calcium ionophore A23187 also could induce both histamine release and cytotoxic activity. These activities induced by IgE receptor triggering, A23187, and lipopolysaccharide were completely neutralized by preincubation with anti-mouse TNF-rabbit serum, but not with normal rabbit serum. Northern blot analysis using cDNA probe of mouse TNF demonstrated expression of TNF gene as early as 2 h after IgE receptor triggering. These data demonstrating that IgE receptor triggering induced gene expression and production of TNF in lung tissue suggest the participation of TNF in the pathogenesis of late asthmatic response through its biologic activities such as the attraction and activation of neutrophils and eosinophils.
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PMID:Production of tumor necrosis factor with IgE receptor triggering from sensitized lung tissue. 169 98

Phosphotyrosine-containing proteins were detected by western blotting of whole cell lysates of purified human neutrophils or rat basophilic leukemia cells (RBL-2H3) using a polyclonal anti-phosphotyrosine antibody. When either cell type was stimulated with the appropriate Fc crosslinking agent, heat-aggregated IgG for the neutrophil or DNP-HSA for the IgE-sensitized RBL-2H3, a rapid increase in the phosphotyrosine content of several proteins was observed. The kinetics and specificity of both responses suggest that Fc receptor crosslinking activates a receptor-associated tyrosine kinase, probably a member of the src family of tyrosine protein kinases. The subsequent tyrosine phosphorylation events are likely to be important in Fc receptor-mediated stimulus-response coupling in inflammatory cells.
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PMID:Tyrosine phosphorylation is an early signaling event common to Fc receptor crosslinking in human neutrophils and rat basophilic leukemia cells (RBL-2H3). 171 Apr 46

We have determined the specific binding of 2,4-dinitrophenyl (DNP)-haptens to two different monoclonal immunoglobulin (IgE) molecules bound to Fc epsilon-receptors on the cell surface of single, living rat basophilic leukemia cells subclone 2H3 cells. The measurements were performed at 4 degrees, 15 degrees, and 25 degrees C using a recently developed technique that permits the quantitative determination of fluorescence resonance energy transfer between two fluorophores on single cells in a microscope from the photobleaching kinetics of the donor fluorophore. We introduce here a method for performing binding studies on individual attached cells. At 25 degrees C, the titration studies yielded equilibrium binding constants Kint of 9 x 10(8), 8 x 10(8), and 8 x 10(7) M-1 for the monovalent haptens N-2,4-DNP-epsilon-amino-n-caproic acid, N epsilon-2,4-DNP-L-lysine, and N-2,4-DNP-gamma-amino-n-butyric acid, respectively. Our data indicate that the affinity constants for the first two haptens binding to IgE on adherent cells are 4 to 11 times larger than that of the corresponding values obtained by fluorescence quenching experiments with the same haptens and IgE molecules either in solution or bound to cells in suspension.
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PMID:Fluorescence resonance energy transfer on single living cells. Application to binding of monovalent haptens to cell-bound immunoglobulin E. 183 74

Serotonin release from rat basophilic leukemia (RBL) cells, sensitized with a DNP-binding monoclonal IgE, was stimulated with solid surface (polystyrene)-bound DNP-amino acids. The stimulatory potency of DNP-amino acids was dependent on the structure of amino acid attached to DNP. Generally, DNP-amino acids with high affinities to the sensitizing IgE (I(50) less than 10 microM) were stimulatory in polystyrene-bound form; DNP-amino acids with lower affinities (Pro, Cys, Trp), and aliphatic aromatic DNP-amino acid derivatives were inactive. In addition to structural analogues of DNP, lymecycline, that is chemically unrelated to DNP but was found to have high affinity to IgE(aDNP), was also stimulatory in this system. This drug, and various quinones (e.g. acenaphthene-quinone) in BSA-conjugated forms also stimulated serotonin release from RBL cells sensitized with IgE(aDNP). These studies suggest that (1) There is a threshold of intrinsic ligand binding affinities at approximately I(50) = 10-100 microM; ligands with lower affinities do not stimulate mediator release even if they are presented in multivalent forms; (2) The above affinity threshold for mediator cell stimulation is valid for various ligands, irrespective of their chemical similarity to the immunogen; (3) Multispecific stimulation of mediator release may contribute to the frequently observed allergic cross-reactions, false positive tests for allergies, and anaphylactic reactions to drugs upon first exposure.
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PMID:Mechanism of allergic cross-reactions--II. Cross-stimulation, by chemically unrelated ligands, of rat basophilic leukemia cells sensitized with an anti-DNP IgE antibody. 186 80

Cross-linking of the IgE receptor on the surface of rat basophilic leukemia cells by multivalent Ag (DNP-BSA) causes a rapid conversion to a detergent-insoluble form. There is a concurrent increase in the amount of filamentous actin associated with the plasma membrane. Both the degree of receptor detergent insolubility and the rise in F-actin content are rapid with a half-maximal response of less than 1 min and can be rapidly reversed by the addition of monovalent Ag (DNP-lysine). These two early steps in the triggering of rat basophilic leukemia cells can be dissociated from each other by pretreatment of the cells with either cytochalasin or sodium azide. These reagents block the increase in F-actin but have no effect on receptor detergent insolubility. This indicates that microfilaments are not responsible for detergent insolubility of the receptor and that it may be the membrane skeleton that is interacting with the complex. This was further confirmed by the finding that cross-linking of the IgE receptors on the surface of purified plasma membranes also leads to detergent insolubility of the receptor. Therefore, all of the components necessary for detergent insolubility of the receptor are present in the plasma membrane, and cytoplasmic components are not needed. These results suggest that detergent insolubility and immobility of the cross-linked receptors are caused by multivalent interaction with the membrane skeleton. Actin filaments may then interact with these receptor-membrane skeletal complexes in order to produce large scale clustering and capping. The membrane skeleton may therefore be acting as an intermediate structure between the cell-surface receptors and microfilaments.
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PMID:Antigen-induced cross-linking of the IgE receptor leads to an association with the detergent-insoluble membrane skeleton of rat basophilic leukemia (RBL-2H3) cells. 214 3

A 22-year-old female was admitted to our hospital because of general fatigue. The lymph nodes, liver and spleen were not palpable. She was without cutaneous lesions. Haematological examinations revealed leukocytes 3,200/microliters with 44% blasts of myelomonocytic origin, and platelets 15,000/microliters. Bone marrow smears were hypercellular marrow with 51% blasts of myelomonocytic origin and focal involvement of mast cells. Serum histamine and vitamin B12 level was high. Mast cells were round with rounded or segmented nuclei. The nucleoli were inconspicuous and the cytoplasm contained a number of metachromatic granules. Cytochemically, mast cells stained positive for alpha-naphthol-AS.D-chloroacetate esterase and acid phosphatase, and negative for peroxidase, Sudan black B and alpha-naphthyl butylate esterase. In toluidine blue staining, mast cells had stained similarly with pH values from 2.5 to 6.5. She was diagnosed as acute myelomonocytic leukemia with benign mastocytosis, and treated with BH.AC-DNP. A complete remission was obtained, but mast cells in the marrow did not decrease. Relationship between leukemia and mastocytosis was not known, but it was suggested that mast cells responded to the proliferation of the leukemic cells.
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PMID:[Acute myelomonocytic leukemia with mastocytosis in bone marrow]. 232 87

A simple and sensitive assay for screening mouse IgE-producing hybridomas is described. Rat basophil leukemia (RBL) cells (either live or glutaraldehyde fixed) were sensitized by mouse monoclonal IgE and then rosetted with antigen-coated sheep red blood cells. The assay was established using a mouse monoclonal IgE anti-DNP and was able to detect as little as 5 ng/ml IgE. The rosette assay is also a useful technique for studying the binding of mouse IgG monoclonal (MC) antibodies to RBL cells.
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PMID:A novel in vitro assay for mouse IgE. 240 74

The role of the Fc epsilon, receptor (Fc epsilon R), isolated from rat basophilic leukemia cells (line RBL-2H3) in antigen induced Ca++ channel opening has been studied by following ion conductance in reconstituted model membranes. Planar bilayers were constructed from lipid vesicles containing the purified Fc epsilon R alone, or together with the cromolyn binding protein (CBP). Changes in conductivity of these bilayers were measured as a monitor for channel activity, following specific aggregation of Fc epsilon R. Antigen-induced, Fc epsilon R mediated channel activity could only be elicited in membranes containing both proteins. This conductance was abrogated upon disaggregating the complexes with a monovalent hapten (epsilon-N-DNP-L-lysine). No channel activity was observed following antigen-induced aggregation of Fc epsilon R if CBP was not present in the bilayer. The single channels recorded were of approximately equal to 2 pS conductance. The open-time values varied significantly with individual experiments and depended on the protein composition of the membrane and the nature of the aggregating agent. These observations strongly indicate that the Fc epsilon R isolated from RBL cells does not form cation (Ca++) channels by itself. Furthermore, in line with earlier reports, the present data suggest that the CBP is responsible for this activity, and that it interacts directly with Fc epsilon R to open channels upon aggregation.
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PMID:The role of the Fc epsilon receptor in calcium channel opening in rat basophilic leukemia cells. 242 Jul 15


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