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 established a T-cell line, STO-2, by human T-cell lymphoma-leukemia virus-induced transformation of normal human T cells. Partial purification with isoelectric electrophoresis revealed that STO-2 liberated several eosinophil chemotactic factors (ECF) for eosinophils from healthy individuals with different isoelectric point of PI5, PI6, PI7, PI8, and PI9. Molecular weight of all the ECF was about 30,000 to 45,000. None of the ECF except ECF-PI5 was suppressed when they were incubated with monoclonal antibodies against IL-3, IL-5, and GM-CSF together, suggesting that ECF activity of ECF-PI5 is mainly comprised of IL-3, IL-5, and GM-CSF. ECF-PI5, PI6, and PI7 also exhibited enhancing activity on ex vivo eosinophil survival whereas ECF-PI8 and PI9 failed. Expression of Fc epsilon receptor II on eosinophils was potentiated by ECF-PI6 and ECF-PI7. In contrast, expression of Fc gamma receptor III was potentiated by ECF-PI7, ECF-PI8, and ECF-PI9. ECF-PI6 could also change an eosinophilic cell line, EOL-1, to eosinophilic granule-positive cells, whereas the rest of ECF failed. The above results suggested that eosinophils attracted by an ECF exhibit their biological functions, which differ from those of eosinophils attracted by other ECF. In further experiments, the chemotactic response of eosinophils from patients with eosinophilia was compared to that of eosinophils from healthy individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Establishment of a human T-cell line constitutively producing several eosinophil chemotactic lymphokines and their functional heterogeneity on eosinophils. 133 63

The high-affinity receptor for IgG, Fc gamma RI, expressed on monocytes and interferon-gamma (IFN-gamma)-stimulated neutrophils, is a trigger molecule for cell-mediated cytotoxicity. We have prepared murine monoclonal antibodies (MoAb 22 and MoAb 32) that bind to Fc gamma RI outside the ligand binding site and thus bind to and trigger cytotoxicity that is not competed by other immunoglobulins. Because of these properties, it seemed that these MoAbs would be very useful for the development of bispecific antibodies (BsAb) for targeting normal cellular immune defense mechanisms as a new form of immunotherapy for treatment of cancer. BsAbs incorporate into a single molecule the binding specifities of two different antibodies, and, thus, can be used to target myeloid cells to tumors, ensure activation of cellular cytotoxic mechanisms, and target cell lysis and/or phagocytosis. BsAbs were prepared using anti-Fc gamma RI MoAb and an anti-myeloid cell MoAb, PM81, reactive with the CD15 antigen, for studies of antibody-dependent cellular cytotoxicity. Conjugates were made by cross-linking sulfhydryl groups of Fab fragments of MoAb 32 or 22 (both IgG1) and sulfhydryl groups added to intact PM81 (an IgM) using N-succinimdyl-acetyl-S-thioacetate (SATA). The resulting product was purified by high-performance size-exclusion chromatography. The ability of the BsAbs to mediate attachment of human monocytes to tumor target cells was confirmed in a microtiter well assay of binding of MTT-labeled U937 cells (a human Fc gamma RI-bearing cell line) to SKBR-3 (PM81-reactive breast carcinoma) target cells. The ability of the BsAbs to mediate killing of HL-60 promyelocytic leukemia cells was studied using a 6-hour Chromium-51 release assay. Effector cells were monocytes obtained by cytopheresis and cultured for 18 hours with IFN-gamma. Monocytes alone caused minimal killing (5-20%), monocytes plus BsAb caused moderate killing (20-50%), and monocytes plus BsAb plus human serum resulted in maximal killing (50-80%). Experiments were performed to test the ability of the BsAb to purge bone marrow of small numbers of leukemia cells using bone marrow mononuclear phagocytes treated for 18 hours with IFN-gamma prior to adding target cells. Without the addition of human serum as a source of complement, a 90% depletion of clonogenic HL-60 cells could be demonstrated. With human complement, up to 95% depletion was seen. Thus, this BsAb possessed the ability to lyse tumor cell targets by two different mechanisms, complement and cell-mediated lysis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Initial trial of bispecific antibody-mediated immunotherapy of CD15-bearing tumors: cytotoxicity of human tumor cells using a bispecific antibody comprised of anti-CD15 (MoAb PM81) and anti-CD64/Fc gamma RI (MoAb 32). 136 20

Astrocytes have been regarded as the matrix of the central nervous system and as nutritional, metabolic support to neurons. Recently, immunological roles of astrocytes have been reported, especially in multiple sclerosis and experimental allergic encephalitis. One observation shows that human glioma cells, which lack CD4 molecules, can be infected with human immunodeficiency virus in vitro. Another report described that human macrophages can be infected with human immunodeficiency virus through Fc gamma receptors expressed on their cell surfaces. These results prompted us to examine the functioning molecules, especially Fc gamma receptor for immunoglobulin G, expressed on the astroglial cell line. From erythrocyte-antibody rosette assays, redirected cytolysis and flow cytometric analysis, we have shown that human astrocytoma cell lines possess Fc gamma receptors on their cell surfaces. Furthermore, primary cultured murine astrocytes express Fc gamma II receptors, reacting with 2.4G2 monoclonal antibody. Surprisingly, murine astrocytes prepared from newborn BALB/c mice demonstrate killing activity against allogeneic T cell leukemia by antibody-dependent cellular cytotoxicity. After treatment with the macrophage activating factor, interferon-gamma, expression of Fc gamma receptors and killer activity of astrocytes were augmented. From these results, it is suspected that the astroglial cell lines play an important immunological role in the brain.
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PMID:Expression of Fc gamma receptors on astroglial cell lines and their role in the central nervous system. 138 16

Murine mast cells produce cytokines in response to cross-linking of high affinity receptors for IgE (Fc epsilon RI). Murine mast cells also express the two types of low-affinity receptors for IgG, murine (m)Fc gamma RII, and mFc gamma RIII. We examined the ability of mFc gamma R to trigger a cytokine response such as TNF-alpha production by mast cells. We found that the mFc gamma RII- and mFc gamma RIII-positive mouse mastocytoma cells MMC-1 released TNF-alpha when challenged with F(ab')2 fragments of the rat anti-mFc gamma RII/III 2.4G2 mAb and mouse anti-rat IgG F(ab')2. The release of TNF-alpha was preceded by an increase in TNF-alpha transcripts. mFc gamma RII and mFc gamma RIII have 95% homologous extracellular domains but unrelated transmembrane and intracytoplasmic (IC) domains. mFc gamma RII are single chain receptors whereas mFc gamma RIII associate with a homodimeric gamma-chain that also associates with Fc epsilon RI and TCR. In order to analyze the ability of mFc gamma RII and III to trigger the synthesis of TNF-alpha, we studied RBL-2H3 cells transfected with corresponding cDNA. Rat basophilic leukemia (RBL) transfectants expressing mFc gamma RIII produced TNF-alpha in response to 2.4G2 F(ab')2, but not transfectants expressing mFc gamma RII. Non-transfected RBL cells and mFc gamma RII- or mFc gamma RIII-expressing transfectants, however, released TNF-alpha in response to a rat IgG2a mAb. The respective roles of the alpha and gamma subunits of mFc gamma RIII were examined by studying the production of TNF-alpha by RBL cells expressing deletant and chimeric mFc gamma R. The deletion of intracellular amino acids of the Fc gamma RIII alpha subunit did not prevent 2.4G2 F(ab')2 from triggering the synthesis of TNF-alpha. The substitution of the IC domain of mFc gamma RII for that of mFc gamma RIII gamma, but not that of Fc gamma RIII alpha, enabled 2.4G2 F(ab')2 to trigger the release of TNF-alpha by RBL transfectants. A cytokine response can therefore be induced in mouse and rat mast cells through Fc gamma R. This response is triggered upon cross-linking of mFc gamma RIII but not mFc gamma RII. It depends on the IC sequences of the gamma but not of the alpha subunit of mFc gamma RIII.
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PMID:Induction of tumor necrosis factor-alpha production by mast cells via Fc gamma R. Role of the Fc gamma RIII gamma subunit. 138 72

The cellular responses initiated by cross-linking rodent Fc gamma RII-b1, Fc gamma RII-b2, Fc gamma RIII, and Fc epsilon RI in mast cells were compared. Individual murine Fc gamma R isoforms were transfected into rat basophilic leukemia cells and after cross-linking the FcR, changes in the phosphorylation of protein tyrosines, in the level of intracellular Ca2+, in the hydrolysis of phosphoinositides, and in the release of arachidonic acid metabolites and hexosaminidase were monitored. Cross-linking of Fc gamma RIII initiated all of these early and late biochemical functions, and although they were quantitatively somewhat smaller, the responses were qualitatively indistinguishable from those stimulated by the endogenous Fc epsilon RI. However, despite ample expression, neither Fc gamma RII-b1 nor Fc gamma RII-b2 stimulated these functions when cross-linked. The functional differences between Fc gamma RII and Fc gamma RIII were studied further by assessing the responses to cross-linking of the endogenous Fc gamma R (Fc gamma RII-b1, Fc gamma RII-b2, and Fc gamma RIII) on P815 mouse mastocytoma cells that had been transfected with normal or functionally defective Fc epsilon RI. Two types of mutant subunits had previously been observed to impair the activity of Fc epsilon RI: gamma-chains missing the cytoplasmic domain, and beta-chains missing the COOH-terminal cytoplasmic domain. In both types of transfectants the functional inhibition of the endogenous Fc gamma R paralleled that of the transfected Fc epsilon RI. These results are consistent with the gamma subunit being associated with the functions of Fc gamma RIII as well as of Fc epsilon RI. The functional results also complement the recently reported evidence that Fc gamma RIII can interact with Fc epsilon RI beta-subunits (J. Exp. Med. 175:447, 1992).
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PMID:Functional comparison of Fc epsilon RI, Fc gamma RII, and Fc gamma RIII in mast cells. 138 91

The three forms of Fc gamma receptor carried by monocytes (Fc gamma RI, II) and natural killer (NK) cells (Fc gamma RIII) are all capable of mediating cell lysis. Here we compare the use of F(ab'gamma)2 bispecific antibodies, specifically targetting individual Fc gamma R, and chimeric IgG mouse/human antibodies which are capable of targetting all Fc gamma R, for their ability to mediate target cell destruction. The derivatives are prepared by linking hinge sulphydryl residues via tandem thioether bonds, using a bismaleimide crosslinker: Fab' from an anti-Fc gamma R mAb linked to Fab' from a common anti-target mAb (BsAb), or Fab' from the common anti-target mouse antibody linked to human Fc gamma (FabFc or bisFabFc). All the derivatives targetting chick red blood cells gave efficient lysis, although different effector cell donors yielded differences in both the lytic levels achieved and the comparative efficiencies of derivatives. In contrast, significant lysis of the guinea pig lymphoblastic leukaemia, L2C, regularly resulted only via the anti-Fc gamma RIII BsAb and the chimeric derivatives. These results suggest that the chimeric, Fc-containing derivatives mediate tumour cell lysis principally through Fc gamma RIII on NK cells. This is in contrast to the situation with the chick red blood cells where the chimeric derivatives appear capable of lysing erythrocytes by utilizing either monocytes or NK cells, because significant (approximately 50%) lysis occurred with effector cell populations magnetically depleted through either Fc gamma RII or Fc gamma RIII. A major difference between these two types of antibody derivative was their ability to function in the presence of high concentrations of normal human Fc gamma. The lysis mediated by BsAb reactive with Fc gamma RI or II was unaffected by the presence of human Fc gamma at 2.5 mg/ml (a concentration comparable with that yielded by IgG in plasma) whereas the BsAb recognizing Fc gamma RIII and all the Fc-containing derivatives were completely inhibited.
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PMID:Comparative efficiencies of bispecific F(ab'gamma)2 and chimeric mouse/human IgG antibodies in recruiting cellular effectors for cytotoxicity via Fc gamma receptors. 153 22

Phenotypes of cells from 12 patients with acute myelogenous leukemia (AML) were analysed by means of a fluorescence-activated cell sorter utilizing a panel of monoclonal antibodies (MAbs). A majority of the cells from peripheral blood coexpressed the antigens against MAbs CD11, CD13, and CD33 but did not express the antigens against CD1, CD3, CD4, CD5, CD8, CD19, CD20, CD21, CD41 and 42, and glycophorin A. Three out of the 12 cases expressed CD7 antigen. However, one of them showed no reaction with Tp40 MAb, whereas the others showed reaction with Leu9 and T55. The discrepancy of reactivities between Leu9 and Tp40 MAbs prompted us to study the promyelocytic leukemia cell line HL-60, which showed similar reactions against Leu9 and Tp40 MAbs. Leu9, OKT16, and T55 MAbs reacted strongly with HL60 cells, whereas Tp40 MAb, which reacted strongly with T-cell leukemia cell line Jurkat, showed no reaction. The reactivity of Leu9, OKT16, and T55 MAbs with HL-60 cells was completely inhibited after preincubation with aggregated human immunoglobulin G (AHIG), which clearly shows the existence of nonspecific binding between these 3 MAbs and HL-60 cells via Fc gamma R. On the basis of our experiments, we conclude that HL-60 cells bind nonspecifically with Leu9, OKT16, and T55 MAbs via FcRI, and this is suggestive that de novo AML cells probably behave in the same fashion. Hence, we recommend that the utilization of murine IgG2a and IgG3 MAbs should be avoided especially in cell surface analysis of myeloid leukemic cells.
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PMID:CD7 false-positive acute myelogenous leukemia and promyelocytic leukemia cell line HL-60: characterization of CD7 epitopes by four monoclonal antibodies. 171 52

Morphological and functional characteristics of a permanent human leukemia cell line (DD) that possesses myelomonocytic features were investigated. The cells bear a second type Fc gamma receptor and form rosettes with sheep erythrocytes sensitized with rabbit IgG (EA). However, the surface-bound EA is not internalized. The cell line lacks the surface markers CD2, CD19, CD14, HLA-DR, Fc gamma receptor I, Fc gamma receptor III, and CR3. alpha 1-Antitrypsin, lysozyme, Factor XIII a subunit of blood coagulation, and acid phosphatase reactions were negative. A terminal differentiation of the DD cell line was observed when the expression of CD14, CR3, Fc gamma receptor I, and Fc gamma receptor III was induced. The DD cells induced with 12-O-tetradecanoylphorbol-13-acetate or Escherichia coli lipopolysaccharide can internalize EA via Fc gamma receptor II and complement-coated yeast in the function of the inducers. The phagocytic ability appears to be parallel with the appearance of enzymes which participate in phagocytosis.
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PMID:Marker profile, enzyme activity, and function of a human myelomonocytic leukemia cell line. 173 17

We investigated the effects of interferon-gamma (IFN-gamma), phorbol myristate acetate (PMA), and dibutyryl cAMP (Bt2cAMP) on Fc gamma R subtype expression on a human eosinophilic leukemia cell line, EoL-3. Unstimulated EoL-3 cells expressed Fc gamma RII as determined by monoclonal antibody (mAb) IV-3, whereas there was little or no Fc gamma RI and Fc gamma RIII expression as determined by mAbs 32.2 and 3G8, respectively. IFN-gamma induced Fc gamma RI expression, and Bt2 cAMP, which did not induce Fc gamma RI expression by itself, showed an additive effect on IFN-gamma-induced Fc gamma RI expression. Fc gamma RII expression was augmented by IFN-gamma, PMA, and Bt2 cAMP. Bt2 cAMP also showed an additive effect on IFN-gamma-augmented Fc gamma RII expression. Fc gamma RIII expression could be induced only by IFN-gamma plus Bt2 cAMP. H-7, a protein kinase C (PK-C) inhibitor, suppressed the enhancement of Fc gamma R subtype expression induced by these reagents. These results show that Fc gamma R subtype expression on EoL-3 cells is regulated differently in each subtype and that cAMP and PK-C play important roles in the regulation.
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PMID:Regulation of Fc gamma receptor subtype expression on a human eosinophilic leukemia cell line EoL-3: participation of cAMP and protein kinase C in the effects of interferon-gamma and phorbol ester. 184 82

The close relation between rat mast cells and rat basophilic leukemia (RBL) cells with regard to the presence of receptors for IgE and Fc gamma led us to generate monoclonal antibodies directed against cell surface antigens. Hybridomas were obtained by the fusion of NS1 mouse myeloma cells with murine spleen and lymph node cells. The culture supernatants were assayed by two ELISA techniques: a) for the production of mouse immunoglobulin in general and b) for antibodies directed against surface antigens of RBL cells. For this purpose RBL cells were attached to polyvinyl chloride microtitre plates. Eight hybrids produced antibodies directed against surface antigens on RBL cells. Hybrids were cloned and characterized with regard to their isotype and light chains. All eight clones secreted IgM with K light chains. Immunofluorescence studies performed with RBL cells revealed that all eight antibodies were able to show a specific fluorescence. Furthermore, four of these eight antibodies also showed a specific fluorescence with purified rat mast cells. These four antibodies were analyzed as to their ability of interacting with the IgE-receptor on RBL cells and purified rat mast cells. They reduced the binding rate of radiolabelled rat IgE to RBL and rat mast cells. A mutual inhibition of the passive cutaneous anaphylaxis (PCA) reaction in the rat by either mixing mouse reaginic serum directed against 2,4-dinitrophenol bovine serum albumin (DNP-BSA) or by mixing monoclonal mouse anti-DNP IgE with the monoclonal mouse anti-cell surface (rat basophilic leukemia, rat mast cell) IgM was determined.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction of monoclonal antibodies with the IgE-receptor on rat mast cells and rat basophilic leukemia (RBL) cells. 242 99


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