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

Murine low-affinity Fc receptors for IgG (Fc gamma RIIb 1, Fc gamma RIIb2, and Fc gamma RIII) bind the same IgG subclasses and are not distinguished by available anti-Fc gamma RII/III mAbs (2.4G2). They trigger various biological activities, among which are the internalization of soluble and particulate immune complexes, cell activation, and its regulation. To determine the biological properties of the three murine receptors, each was expressed by stable transfection of corresponding cDNAs in two model cells: the murine lymphoma B cell IIA1.6 and the rat basophilic leukemia cell RBL-2H3. Biological activities of recombinant receptors were triggered with soluble immune complexes or 2.4G2 IgG in IIA1.6 cells, which express no Fc gamma R, and with 2.4G2 Fab or F(ab')2, cross-linked with mouse anti-rat F(ab')2 in RBL, which express rat Fc gamma R. Conditions for studying cell activation and endocytosis in both cell models are described, as are conditions for studying phagocytosis in RBL cells and antigen presentation or regulation of cell activation in IIA1.6 cells. Internalization of immune complexes was triggered by Fc gamma RIIb2 and Fc gamma RIII, but not by Fc gamma RIIb1. Intracytoplasmic sequences required for phagocytosis and endocytosis could be distinguished in Fc gamma RIIb2, but not in Fc gamma RIII. Cell activation was restricted to Fc gamma RIII. Fc gamma RIII-mediated endocytosis, phagocytosis, and cell activation involved the consensus tyrosine-containing activation motif found in the intracytoplasmic domain of the gamma subunit. Regulation of cell activation was induced by both Fc gamma RII isoforms and depended on the same sequence as endocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biological activities of murine low-affinity Fc receptors for IgG. 806 27

Recently, a human eosinophilic leukemia cell line, EoL was established from an eosinophilic leukemia patient. EoL-1 cells have the cytohistologic features of myeloblasts under normal culture conditions, and they can be induced to differentiate into eosinophilic granule-containing cells but not into other lineage cells under several culture conditions and are therefore considered to be committed precursors of eosinophils. Furthermore, EoL-1 cells can also be induced to differentiate functionally to show PAF-induced Ca2+ influx and actin polymerization. On the other hand, EoL-3 cells show constitutive expression of Fc epsilon RII, Fc gamma RII, LFA-1 and ICAM-1 on their cell surface. The EoL cells may provide new information on some aspects of the signal transduction mechanisms involved in the proliferation, differentiation and activation of eosinophils.
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PMID:[Review: recent studies on a human eosinophilic leukemia cell line, EoL as an experimental model of eosinophils]. 809 79

FcR capable of triggering cell activation share with BCR and TCR a conserved intracytoplasmic tyrosine-containing activation motif (TAM). Besides cell activation, these receptors trigger other biologic responses, such as endocytosis of soluble ligands. Murine mast cells express two types of FcR that, when aggregated by antibodies and multivalent Ag, trigger the release of inflammatory mediators and cytokines. These are high affinity receptors for IgE (Fc epsilon RI) and low affinity receptors for IgG (Fc gamma RIII). They comprise each an IgE- or IgG-binding alpha-subunit and two TAM-containing subunits that associate with both receptors: a beta-subunit and a homodimeric gamma-subunit that can associate also with the other subunits of the TCR. Herein, we focused on biologic activities triggered in mast cells via the TAM of the gamma-subunits. Using rat basophilic leukemia (RBL) cells stably transfected with cDNA-encoding murine Fc gamma RIII alpha, we found that murine Fc gamma RIII trigger the phagocytosis of antibody-coated erythrocytes. Using RBL transfectants expressing Fc gamma RIII with a deletion of the intracytoplasmic domain of Fc gamma RIII alpha or chimeric receptors having the extracellular and transmembrane domains of Fc gamma RII and the intracytoplasmic domain of Fc gamma RIII alpha, we showed that intracytoplasmic sequences of Fc gamma RIII alpha are neither necessary nor sufficient for Fc gamma RIII to trigger phagocytosis. Using RBL transfectants expressing chimeric receptors having the extracellular and transmembrane domains of Fc gamma RII and the TAM-containing intracytoplasmic domain of murine Fc gamma RIII gamma, we demonstrated that intracytoplasmic sequences of Fc gamma RIII gamma are sufficient to trigger phagocytosis. Using RBL transfectants expressing the same Fc gamma RII-III gamma chimeras, in the TAM of which one, the other, or both tyrosine residues were mutated, we established that tyrosines in the TAM sequence are required for phagocytosis. Our results endow TAM gamma with previously unknown triggering capacities and Fc gamma RIII with new biologic properties.
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PMID:Tyrosine-containing activation motif-dependent phagocytosis in mast cells. 828 51

Fc gamma RIII is a low affinity immunoglobulin G receptor expressed by neutrophils, natural killer cells, and macrophages. Soluble forms of Fc gamma RIII have been identified in serum, plasma, and other body fluids. Previous studies showed that Fc gamma RIII appeared late in myeloid differentiation. This retrospective study was designed to measure the concentration of soluble Fc gamma RIII in serum from patients with acute myelogenous leukemia (AML), a disease generally characterized by granulocytopenia and an increase in circulating myeloblasts and occasionally promyelocytes. Frozen serum samples from patients with AML and from age-matched normal donors were obtained from the Biological Carcinogenesis Branch Repository of the National Cancer Institute. We used an ELISA to measure the concentration of soluble Fc gamma RIII in these serum samples and observed significantly lower concentrations of soluble Fc gamma RIII in the serum of AML patients. The mean concentration of soluble Fc gamma RIII was 9.5 nM in normals (n = 48) and 5.4 nM in AML patients (n = 46), (p < 0.0005). Whether this difference is due to defects in granulopoiesis in these patients or to other parameters of the disease is unknown at this time. Our retrospective study should provide the basis for subsequent investigation of patients with AML to correlate soluble Fc gamma RIII concentrations with the clinical status of the patients.
Leukemia 1993 Aug
PMID:Soluble Fc gamma RIII is present in lower concentrations in the serum of patients with acute myelogenous leukemia (AML): a retrospective study. 835 Jun 25

We have investigated the effects of 1,25-dihydroxyvitamin D3 (D3) and/or transforming growth factor (TGF)-beta on one monocytic (U-937) and two human promyelocytic (HL-60 and AML-193) leukemic cell lines. D3 addition induces a partial monocytic maturation of the cell lines, whereas TGF-beta treatment is largely ineffective. Combined treatment with TGF-beta and D3 causes terminal monocytic maturation, as evaluated both by assessment of a large spectrum of membrane Ag and by functional assays. Furthermore, sequential addition of the two inducers showed that pretreatment with TGF-beta 1 followed by incubation with D3, but not vice versa, induces monocytic maturation as effectively as simultaneous treatment with both agents. In liquid culture the proliferative activity of these cell lines is slightly decreased by D3 and virtually unaffected by TGF-beta, whereas combined treatment with D3 and TGF-beta induces a markedly potentiated inhibitory effect. Furthermore, TGF-beta/D3 treatment (but not D3 alone) elicits the expression of membrane CD14, FcRI, FcRII, CD11a, CD11b, CD11c, ICAM-1, and PECAM-1 Ag at a level comparable to that observed on normal human monocytes. It is noteworthy that several of these Ag play an important role in monocyte physiology (e.g., CD14 Ag mediates the binding of bacterial LPS to monocytes). Treatment with both TGF-beta and D3 (but not D3 alone) induces superoxide anions and H2O2 production similar to that of circulating monocytes. In semisolid culture, D3 and TGF-beta alone cause, respectively, a marked and slight loss of cloning efficiency of the cell lines, whereas their combined addition synergistically results in a complete loss of the cloning capacity. These findings suggest a physiologic role for TGF-beta in monocyte maturation. Furthermore, they may pave the way to the design of clinical protocols combining D3 and TGF-beta in the differentiation therapy of acute promyelocytic/myelomonocytic leukemia.
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PMID:Transforming growth factor-beta potentiates vitamin D3-induced terminal monocytic differentiation of human leukemic cell lines. 838 19

The expression of Fc gamma receptor III (Fc gamma RIII) on a human eosinophilic leukemia cell line, EoL-1, was examined and compared with its expression on normal blood eosinophils. Surface Fc gamma RIII expression on EoL-1 cells could be induced in vitro with a combination of dibutyryl cAMP (dbcAMP) and gamma-interferon (IFN-gamma), but not with IFN-gamma or dbcAMP alone. Pretreatment of EoL-1 cells with dbcAMP induced EoL-1 cells to express Fc gamma RIII when stimulated with IFN-gamma, but EoL-1 cells pretreated with IFN-gamma and then stimulated with dbcAMP failed to express Fc gamma RIII. Cyclic AMP was shown to play a role in the effect of dbcAMP. Both the treatment with phosphatidyl-inositol-specific phospholipase C (PI-PLC) and the restriction enzyme digestion of Fc gamma RIII cDNA showed that the Fc gamma RIII on EoL-1 cells was a phosphatidylinositol-linked form. On the other hand, freshly isolated blood eosinophils constitutively expressed few, if any, Fc gamma RIII, and IFN-gamma induced Fc gamma RIII expression on them in vitro. Dibutyryl cAMP did not induce Fc gamma RIII expression and even suppressed the IFN-gamma-induced Fc gamma RIII expression on normal eosinophils. The EoL-1 cell line appears to be a useful in vitro model for the expression and function of the phosphatidylinositol-linked form of Fc gamma RIII on eosinophils.
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PMID:Induction of phosphatidylinositol-linked Fc gamma receptor III expression on an eosinophilic cell line, EoL-1, by dibutyryl cyclic AMP and interferon-gamma. 839 82

In this study, Fc gamma receptors (Fc gamma R) on the cells of human megakaryoblastic leukaemia cell lines (Meg-01 and UT-7) were investigated. Binding of the anti-Fc gamma RII monoclonal antibody (MoAb) IV. 3 but not anti-Fc gamma RI MoAb (32.2), anti-Fc gamma RIII MoAb (3G8) nor control murine IgGs to Meg-01 and UT-7 cells was demonstrated by immunocytochemical staining and flow cytometric analysis. There was specific and saturable binding of 125I-labelled IV.3 Fab fragments to the megakaryoblasts but no binding of 125I-labelled 32.2 Fab nor 3G8 Fab fragments. MoAb IV.3 immunoprecipitated a 40 kD protein (Fc gamma RII) from detergent cell lysates of surface radiolabelled Meg-01 and UT-7 cells. More importantly, IV.3 Fab almost completely inhibited the binding of 125I-labelled human aggregated IgG to the Meg-01 cells. In contrast, neither 32.2 Fab, 3G8 Fab nor Fab fragments of the control murine IgGs were inhibitory. These results indicate that only Fc gamma R Type II is expressed on megakaryoblasts in these two cell lines.
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PMID:Identification of IgG Fc receptor type II on human megakaryoblastic cell lines (MEG-01 and UT-7). 839 19

Several new rat class III Fc gamma R isoforms are described here, extending the genetic complexity of this receptor family and further distinguishing rat CD16 from mouse CD16, represented by only one receptor isoform, and human CD16, represented by only two isoforms. RNase protection assays reveal that three rat tumor cell lines--RBL-1 basophilic leukemia cells, RM-SV1 macrophages, and CRNK-16 NK cells--all coordinately express multiple and probably identical rtFc gamma RIII-related transcripts in similar relative proportions but at significantly different levels. These results indicate that no single isoform predominates in these cell types but that the overall level of rtFc gamma RIII-related transcripts is differentially regulated. Two of the rtFc gamma RIII isoforms found to have extensive amino acid sequence differences in their second extracellular (EC2) domains are shown to bind rat and mouse IgG subclasses differently. This result suggests that the receptor isoform diversity in this species may function as a mechanism for extending the IgG-binding capacity of rat leukocytes. Cloned cDNA for the rat CD3 zeta protein was also isolated in this study and its ability to augment surface expression of class III Fc gamma R was tested by rosetting of cDNA-transfected COS cells. Like the structurally homologous mouse CD3 zeta, rat CD3 zeta fails to promote surface expression of Fc gamma RIII, sharply contrasting the efficient receptor expression produced by human CD3 zeta. Variations in the transmembrane amino acid sequences correlate with the divergent capacities of these CD3 zeta molecules to augment receptor expression. The high levels of CD3 zeta message expressed in rat NK cells may indicate that other unidentified hetero-subunits are required for assembly of rat CD3 zeta into functional CD16 receptors.
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PMID:Rat class III Fc gamma receptor isoforms differ in IgG subclass-binding specificity and fail to associate productively with rat CD3 zeta. 848 40

Human blood basophils selectively express Fc gamma RII (CDw32) among IgG receptor subtypes, but its functional role in allergic reactions remains unknown. Using the human basophilic leukemia cell line KU812F as a model system, we investigated cellular signaling events mediated through IgG receptor stimulation. KU812F cells express Fc gamma RII on their surface. mRNAs for both Fc gamma RIIA and IIB subtypes were detected by reverse transcriptase-PCR analysis. In this cell line, Fc gamma RII stimulation induced mobilization of free intracellular calcium and actin polymerization. Yet, no significant histamine release was observed, nor did blood basophils stimulated by anti-Fc gamma RII monoclonal antibody IV.3 and by a secondary antibody release histamine. These data indicate that Fc gamma RII stimulation induces cellular signaling events such as calcium mobilization in human basophils. However, these events do not lead to histamine release.
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PMID:Signal transduction by IgG receptors induces calcium mobilization, but not histamine release, in the human basophilic cell line KU812F. 852 47

Stimulation of the CD40 antigen on normal B cells by crosslinking of anti-CD40 mAbs via their Fc receptor using a Fc gamma RII(CD32)-transfected mouse fibroblast cell line ('CD40 system') results in activation and proliferation. Not only normal B cells, but also malignant B cells fitting in the low-grade malignancy category such as chronic lymphocytic leukemia (CLL), hairy cell leukemia and follicular lymphoma could be induced to proliferation upon CD40 stimulation. Here, the 'CD40 system' has also been used to culture intermediate and high grade malignancies. Proliferation was measured by 3H-thymidine incorporation and cell counting after culture. Time curves showed that at day 7 most cultures were optimal. By flow cytometry, morphology and assessment of light chain restriction the monoclonal nature of the cultured B cells was proven. We confirmed that B cell malignancies with a more slowly evolving course, such as CLL (n=11), PLL (n=5), and low-grade NHL (immunocytoma and follicular cb/cc n=9), could successfully be cultured in the 'CD40 system'. In contrast, four out of seven cases of mantle cell lymphoma did not proliferate. Cases of precursor B lineage ALL (n=7), high grade NHL (n=3) and multiple myeloma (n=10) showed a heterogenous growth pattern. We conclude that the 'CD40 system', although not always successful, is a useful tool to culture a whole variety of B cell malignancies.
Leukemia 1996 Mar
PMID:Proliferation of B cell malignancies in all stages of differentiation upon stimulation in the 'CD40 system'. 864 67


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