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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antigen (Ag)-stimulated phospholipase D (PLD) activation and secretion were almost abolished by pretreatment of rat basophilic leukemia (RBL)-2H3 cells for 4 h with 5 ng/ml Clostridium difficile Toxin B which is known to inhibit Rho family proteins (Rho, Cdc42, Rac). The concentration-dependent inhibition of PLD activation was well correlated with the level of glucosylation of Rho family proteins. In streptolysin O-permeabilized RBL cells, Toxin B suppressed [3H] phosphatidylbutanol (PBut) formation in response to guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and phorbol 12-myristate 13-acetate (PMA) by 67 and 43%, respectively. The synergistic PLD activation by GTP gamma S and PMA was also reduced by Toxin B by 67%. These results suggest that the IgE receptor-coupled PLD activation is largely mediated by Rho proteins.
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PMID:Effect of Clostridium difficile toxin B on IgE receptor-mediated signal transduction in rat basophilic leukemia cells: inhibition of phospholipase D activation. 870 31

1. HL-60 human leukemia cells are a widely employed model system for the analysis of signal transduction processes mediated via regulatory heterotrimeric guanine nucleotide-binding proteins (G-proteins). HL-60 promyelocytes are pluripotent and can be differentiated into neutrophilic or monocytic cells. 2. HL-60 cells express formyl peptide-, complement C5a-, leukotriene B4 (LTB4)- and platelet-activating factor receptors, receptors for purine and pyrimidine nucleotides, histamine H1- and H2-receptors, beta 2-adrenoceptors and prostaglandin receptors. 3. The major G-proteins in HL-60 cells are pertussis toxin (PTX)-sensitive Gi-proteins (Gi2 > Gi3). Gs-proteins and G-proteins of the Gq-family (e.g., G16) are expressed, too. 4. G-protein-regulated effector systems in HL-60 cells are adenylyl cyclase and phospholipase C-beta 2 (PLC-beta 2) and, possibly, phospholipase D (PLD), nonselective cation (NSC) channels and NADPH oxidase. 5. The expression of signal transduction pathways in HL-60 cells strongly depends on the differentiation state of cells. 6. Formyl peptides, via Gi-proteins, mediate activation of PLC, PLD, NSC channels, NADPH oxidase and azurophilic granule release and are referred to as full secretagogues. In dibutyryl cAMP (Bt2cAMP)-differentiated HL-60 cells, C5a and LTB4 are partial and incomplete secretagogues, respectively. There are substantial differences in the Gi-protein activations induced by formyl peptides, C5a and LTB4. 7. In HL-60 promyelocytes, purine and pyrimidine nucleotides mediate activation of PLC and NSC channels largely via PTX-insensitive G-proteins and induce functional differentiation. In Bt2cAMP-differentiated HL-60 cells, they additionally activate PLD, NADPH oxidase and granule release via PTX-sensitive and -insensitive pathways. ATP and UTP are partial secretagogues. Multiple types of receptors (i.e., P2Y- and P2U-receptors and pyrimidinocyeptors) may mediate the effects of nucleotides in HL-60 cells. 8. Bt2cAMP- and 1 alpha,25-dihydroxycholecalciferol-differentiated HL-60 cells express H1-receptors coupled to Gi-proteins and PTX-insensitive G-proteins. In the former cells, histamine mediates activation of PLC and NSC channels, and in the latter, activation of NSC channels. Histamine is an incomplete secretagogue in these cells. 9. HL-60 promyelocytes express H2-receptors coupled to adenylyl cyclase, PLC, and NSC channels. There are substantial differences in the agonist/antagonist profiles of H2-receptor-mediated cAMP formation and rises in cytosolic Ca2+ concentration, indicative of the involvement of different H2-receptor subtypes. H2-receptors mediate functional differentiation of HL-60 cells. 10. Certain cationic-amphiphilic histamine receptor ligands (i.e., 2-substituted histamines, lipophilic guanidines, and a histamine trifluoromethyl-toluidide derivative) show stimulatory effects in HL-60 cells that are attributable to receptor-independent activation of Gi-proteins.
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PMID:G-protein-coupled receptors in HL-60 human leukemia cells. 874 93

Recent reports have indicated that ADP-ribosylation factor (ARF) plays a role in the regulation of phospholipase D (PLD) activity in the in vitro assay system. Since a fungal metabolite brefeldin A (BFA) is known to interfere with ARF function, the effect of BFA on antigen-induced PLD activation was examined in rat basophilic leukemia (RBL-2H3) cells. BFA inhibited the antigen-induced formation of phosphatidylbutanol (PBut), a specific and stable metabolite produced by PLD activity in a concentration-dependent manner. The maximal inhibition obtained at 10 micrograms/ml of the drug was nearly 70% and further inhibition was not observed at higher concentrations. Ca(2+)-ionophore A23187-mediated PLD activation was also prevented by BFA. In contrast, BFA failed to inhibit PLD activation in response to 4 beta-phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). This indicates that there are BFA-sensitive and BFA-insensitive pathways leading to PLD activation in RBL-2H3 cells and also that the PKC-mediated pathway may be insensitive to BFA treatment, suggesting the existence of PLD isozymes. BFA inhibited Ag-induced serotonin release at a concentration 20-fold lower than that needed for the inhibition of PLD. Moreover, PMA caused a marked production of PBut, but it failed to elicit secretory response. This implies that PLD may be not a crucial element for secretory responses.
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PMID:Brefeldin A inhibits antigen- or calcium ionophore-mediated but not PMA-induced phospholipase D activation in rat basophilic leukemia (RBL-2H3) cells. 887 99

Addition of phenylarsine oxide (PAO) to [3H]oleic acid-labeled rat basophilic leukemia (RBL-2H3) cells gave rise to the remarkable formation of [3H]phosphatidylbutanol (PBut), a specific product of phospholipase D (PLD) activation. Preincubation of cells with 2,3-dimercaptopropanol (DMP) or dithiothreitol (DTT), compounds containing sulfhydryls, prevented PAO-stimulated [3H]PBut formation, indicating that PAO-stimulated PLD through interacting with vicinal thiol groups. Treatment of cells with PAO resulted in increase in intracellular Ca2+ concentration without significant production of inositol phosphates. Removal of extracellular free Ca2+ by chelating with EGTA was found to inhibit [3H]PBut formation by PAO. Incubation of cells with 20 nM phorbol 12-myristate 13-acetate (PMA) for 6 h caused down-regulation of protein kinase C (PKC) alpha and beta isozymes, whereas it had no effect on PKC delta, epsilon and zeta isozymes. Under this condition, decrease in PAO-stimulated [3H]PBut formation was observed to occur with a concomitant decrease in the level of PKC alpha and beta isozymes. These results suggest that a covalent bridge between vicinal thiol groups of cell surface proteins induced by PAO potentiates PLD activation and that PAO-induced PLD activation is regulated by Ca2+ and PKC alpha and/or beta isozymes.
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PMID:Phenylarsine oxide (PAO)-mediated activation of phospholipase D in rat basophilic leukemia (RBL-2H3) cells: possible involvement of calcium and protein kinase C. 887 8

The biochemical signaling mechanisms involved in transducing the effects of interferon-gamma (IFN-gamma) on human leukemia-derived HL-60 cell differentiation are not completely understood. Recent studies established the existence of a sphingomyelin (SM) cycle that operates in response to the action of IFN-gamma on HL-60 cells, but the mechanisms by which IFN-gamma induces the SM hydrolysis remain unexplored. In this study, biochemical events mediating IFN-gamma effects on SM turnover and their specificity and role in HL-60 differentiation were investigated. The activation of the SM cycle by IFN-gamma occurred rapidly, with a decrease of approximately 20% in the SM level observed after 60 minutes with a concomitant increase in ceramide level. Treatment of HL-60 cells with IFN-gamma did not influence the 1,2-diacylglycerol concentration, intracellular Ca2+ concentration, or phospholipase D activity. IFN-gamma stimulated a rapid release of arachidonic acid (AA) from HL-60 cells; the effect was abolished by the pretreatment of cells with pertussis toxin, suggesting a role for a pertussis-toxin-sensitive G protein in IFN-gamma-mediated activation of phospholipase A2 (PLA2). At 4 to 120 hours after the stimulation of the cells with IFN-gamma, a significant increase in the particulate and soluble PLA2 activity was observed, corresponding to an increase in the level of immunoreactive cPLA2 in both cytosol and membrane fractions. The treatment of cells with tyrosine kinase inhibitor herbimycin A completely abolished the effect of IFN-gamma on PLA2 activity in membrane and cytosolic fractions, but had no effect on IFN-gamma-mediated early AA release suggesting dual mechanism of PLA2 activation. Melittin, potent activator of PLA2, and AA mimicked the effect of IFN-gamma on SM hydrolysis. Pretreatment of HL-60 cells with the PLA2 inhibitor, bromophenacyl bromide (BPB), or pertussis toxin abolished the effect of IFN-gamma on SM hydrolysis; exogenous addition of AA overcame the effects of BPB and pertussis toxin. Long-term exposure (5 days) of HL-60 cells to IFN-gamma caused an increase in nitroblue tetrazolium (NBT)-reducing and nonspecific esterase (NSE) activity and induced expression of Fc gamma RI (CD64) without significant effects on cell number, adherence, or phagocytic activity. The treatment of cells with AA or melittin induced NBT, NSE, and CD64 expression to the level similar to that observed with IFN-gamma, and no further increase was observed with the combination of IFN-gamma and AA or IFN-gamma and melittin. Treatment of HL-60 cells with indomethacin, an inhibitor of cyclo-oxygenase, and nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenase, had no effects on IFN-gamma-mediated induction of CD64 expression. These studies indicate a key role for the phospholipase A2/AA pathway, as an early biochemical signal elicited by the occupation of IFN-gamma-receptor, in mediating IFN-gamma induction of the SM cycle and phenotypic changes associated with differentiation of HL-60 along monocytic lineage.
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PMID:Arachidonic acid mediates interferon-gamma-induced sphingomyelin hydrolysis and monocytic marker expression in HL-60 cell line. 897 80

Rat basophilic leukemia cells will adhere to and spread out on fibronectin coated surfaces in an integrin dependent manner. Adhesion and spreading on fibronectin leads to increased degranulation, inositol phosphate production, phospholipase D activation, and increased production of prostaglandin D2 and leukotriene C4 when the cells are activated through the high affinity IgE receptor. Rat basophilic leukemia cells will also adhere to surfaces coated with anti-rat class I antibodies, poly-L-lysine, and a lectin purified from Tetragonolobus purpureas. In all cases, antigen activated cells, which were adherent, displayed increased signaling, degranulation and eicosanoid production as compared to cells which were non-adherent. Cells which adhere to either anti-rat class I antibodies or poly-L-lysine also spread even though this is not mediated through integrins. In contrast, adhesion to the lectin from Tetragonolobus did not cause any appreciable spreading unless the cells were also triggered through the IgE receptor. Cells were also able to bind to fibronectin immobilized on polystyrene beads which mimics adhesion but does not allow spreading. However, these cells exhibited no increased signaling, degranulation, or eicosanoid production. Furthermore, rat basophilic leukemia cells can be modified by incubating them in the presence of biotinylated-phosphatidylserine which becomes incorporated into the membrane. These modified cells will adhere to streptavidin coated plates while unmodified cells will not. However, these modified cells do not spread, even after activation with antigen, and they show no increased degranulation or production of eicosanoids. These results indicate that adhesion itself is not sufficient for upregulation of the cells in response to antigen and that spreading of the cells may be the critical component.
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PMID:Increased degranulation and phospholipase A2, C, and D activity in RBL cells stimulated through FcepsilonR1 is due to spreading and not simply adhesion. 909 51

Activation of phospholipase D (PLD) occurs in response to various stimuli and results from the activity of two isozymes, hPLD1 and hPLD2. PLD activity appears to be involved in several myeloid cell processes during their development and activation, including proliferation of myeloblasts in the bone marrow and secretion, phagocytosis and NADPH oxidase activation, essential functions of differentiated neutrophils. The present work studies PLD characteristics, activity and both isozyme expression during maturation and differentiation of myeloid cells by using three different systems: leukemic myeloblasts at different stages of maturation, terminally differentiated neutrophils ex vivo and four human myeloid cell lines, NB4, HL-60, PLB 985 and U937, induced to differentiate with alltrans retinoic acid (ATRA), a cyclic adenosine monophosphate (cAMP) analogue or both agents together. HL-60, a bipotential cell line has also been differentiated along the granulocytic pathway with DMSO and the monocytic pathway with 1,25-dihydroxy vitamin D3. In all these systems, PLD activity increases with maturation and differentiation whatever the inducer used and the granulocytic or monocytic pathways. Increase in basal activity which reflects the expression during development of both hPLD1 and hPLD2 appears to be mainly related to the former isozyme expression. Association of PLD characteristic changes with maturation and differentiation was also confirmed using two NB4 clones resistant to these processes. Comparison between PLD characteristics in myeloblasts during maturation and differentiation ex vivo and in vitro in the different cell lines demonstrated that NB4 induced to differentiate with ATRA represents the best model for further studies on the specific roles of each PLD isoform in various functions of differentiated myeloid cells.
Leukemia 2000 Dec
PMID:Modifications in phospholipase D activity and isoform expression occur upon maturation and differentiation in vivo and in vitro in human myeloid cells. 1118 1

In order to investigate the underlying mechanism of HCl in oesophagitis, the inflammatory response to HCl was observed in RBL-2H3 mast cells. Rat basophilic leukemia (RBL-2H3) cells were used to measure histamine release, arachidonic acid (AA) release, reactive oxygen species (ROS) and peroxynitrite generation induced by HCl. Exogenous HCl increased the level of histamine release and ROS generation in a dose dependent manner, whereas it decreased the spontaneous release of [3H] AA and the spontaneous production of peroxynitrite. Mepacrine (10 microM), oleyloxyethyl phosphorylcholine (10 microM) and bromoenol lactone (10 microM) did not affect both the level of histamine release and ROS generation induced by HCl. U73122 (1 microM), a specific phospholipase C (PLC) inhibitor did not have any influence on level of histamine release and ROS generation. Propranolol (200 microM), a phospholipase D (PLD) inhibitor, and neomycin (1 mM), a nonspecific PLC and PLD inhibitor, significantly inhibited both histamine release and ROS generation. Diphenyleneiodonium (10 microM), a NADPH oxidase inhibitor, and tiron (5 mM), an intracellular ROS scavenger significantly inhibited the HCl-induced histamine release and ROS generation. These findings suggest that the inflammatory responses to HCl is related to histamine release and ROS generation, and that the ROS generation by HCl may be involved in histamine release via the PLD pathway in RBL-2H3 cells.
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PMID:Histamine release by hydrochloric acid is mediated via reactive oxygen species generation and phospholipase D in RBL-2H3 mast cells. 1243 4

Monosomy 7 and deletions of 7q are recurring leukemia-associated cytogenetic abnormalities that correlate with adverse outcomes in children and adults. We describe a 2.52-Mb genomic DNA contig that spans a commonly deleted segment of chromosome band 7q22 identified in myeloid malignancies. This interval currently includes 14 genes, 19 predicted genes, and 5 predicted pseudogenes. We have extensively characterized the FBXL13, NAPE-PLD, and SVH genes as candidate myeloid tumor suppressors. FBXL13 encodes a novel F-box protein, SVHis a member of a gene family that contains Armadillo-like repeats, and NAPE-PLD encodes a phospholipase D-type phosphodiesterase. Analysis of a panel of leukemia specimens with monosomy 7 did not reveal mutations in these or in the candidate genes LRRC17, PRO1598, and SRPK2. This fully sequenced and annotated contig provides a resource for candidate myeloid tumor suppressor gene discovery.
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PMID:Isolation and analysis of candidate myeloid tumor suppressor genes from a commonly deleted segment of 7q22. 1582 Mar 12

Recently, we have shown that treatment of rat C6 glioma cells with the raft disruptor methyl-beta-cyclodextrin (MCD) doubles the binding of anandamide (AEA) to type-1 cannabinoid receptors (CB1R), followed by CB1R-dependent signaling via adenylate cyclase and p42/p44 MAPK activity. In the present study, we investigated whether type-2 cannabinoid receptors (CB2R), widely expressed in immune cells, also are modulated by MCD. We show that treatment of human DAUDI leukemia cells with MCD does not affect AEA binding to CB2R, and that receptor activation triggers similar [35S]guanosine-5'-O-(3-thiotriphosphate) binding in MCD-treated and control cells, similar adenylate cyclase and MAPK activity, and similar MAPK-dependent protection against apoptosis. The other AEA-binding receptor transient receptor potential channel vanilloid receptor subunit 1, the AEA synthetase N-acyl-phosphatidylethanolamine-phospholipase D, and the AEA hydrolase fatty acid amide hydrolase were not affected by MCD, whereas the AEA membrane transporter was inhibited (approximately 55%) compared with controls. Furthermore, neither diacylglycerol lipase nor monoacylglycerol lipase, which respectively synthesize and degrade 2-arachidonoylglycerol, were affected by MCD in DAUDI or C6 cells, whereas the transport of 2-arachidonoylglycerol was reduced to approximately 50%. Instead, membrane cholesterol enrichment almost doubled the uptake of AEA and 2-arachidonoylglycerol in both cell types. Finally, transfection experiments with human U937 immune cells, and the use of primary cells expressing CB1R or CB2R, ruled out that the cellular environment could account per se for the different modulation of CB receptor subtypes by MCD. In conclusion, the present data demonstrate that lipid rafts control CB1R, but not CB2R, and endocannabinoid transport in immune and neuronal cells.
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PMID:Effect of lipid rafts on Cb2 receptor signaling and 2-arachidonoyl-glycerol metabolism in human immune cells. 1701 79


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