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  • 1
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    Bispecific-armed, interferon gamma-primed macrophage-mediated phagocytosis of malignant non-Hodgkin's lymphoma (1996)
    American Society of Hematology
    Details
    Publication Date: 1996-05-01
    Description: To show that macrophages can be effectively targeted against malignant B cells, bispecific antibodies (BsAb) were constructed from two antibodies having specificity for the high-affinity Fc receptor for IgG (Fc gamma RI/CD64) and the B-cell differentiation antigens CD19 and CD37. Using a flow cytometry-based assay and confocal imaging, we show that these constructs mediated significant phagocytosis of B lymphocytes by macrophages that could be enhanced with interferon gamma (IFN gamma) and IFN gamma in combination with macrophage colony- stimulating factor. BsAb-dependent phagocytosis was triggered through Fc gamma RI and could be blocked only by using F(ab')2 fragments from the parent molecule or by cross-linking Fc gamma RI. BsAb-dependent phagocytosis was not blocked by antibodies to the other Fc receptors, Fc gamma RII and Fc gamma RIII. Because these antibody constructs bind to an epitope outside the Fc gamma RI ligand binding site, we show that autologous serum, polyclonal IgG, and monomeric IgG1 did not block BsAb- dependent phagocytosis, whereas autologous serum and the IgG fractions blocked parent molecule monoclonal antibody-dependent phagocytosis due to the avid binding of monomeric IgG to Fc gamma RI. Finally, BsAb- mediated phagocytosis was effective against the malignant B cells of patients with mantle cell lymphoma, prolymphocytic leukemia, and chronic lymphocytic leukemia. Based on these studies, we propose that BsAbs may provide an effective means of immunomodulation for patients with B-cell malignancies.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 2
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    Differentiation of a human monocytic cell line by 1,25-dihydroxyvitamin D3 (calcitriol): a morphologic, phenotypic, and functional analysis (1984)
    American Society of Hematology
    Details
    Publication Date: 1984-11-01
    Description: Several recent studies have suggested a role for 1,25-dihydroxyvitamin D3 (calcitriol) in myeloid differentiation. We have examined the effects of calcitriol on the U937 monoblast cell line and found that calcitriol, at near physiologic concentrations, is a potent inhibitor of U937 growth. Moreover, calcitriol induces differentiation to a monocyte-macrophage phenotype marked by enhanced alpha-naphthyl esterase staining. Morphologic changes were attended by de novo induction of the myeloid specific antigen detected by the monoclonal antibody AML-2–23, as well as dramatic increases in Fc receptors for IgG. In addition, calcitriol induced U937 cells to perform phagocytosis and antibody-dependent cellular cytotoxicity. These results indicate the potential activity of calcitriol in myeloid differentiation and additionally suggest a role for calcitriol in monocyte-macrophage activation.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 3
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    The expression of myeloid-specific antigens on myeloid leukemia cells: correlations with leukemia subclasses and implications for normal myeloid differentiation (1983)
    American Society of Hematology
    Details
    Publication Date: 1983-03-01
    Description: The expression of three distinct myeloid-specific cell surface antigens detected by monoclonal antibodies (PMN 6, PMN 29, and AML-2–23) on acute and chronic myeloid leukemia cells is correlated with blast cell morphology and normal myeloid cell antigen display. In studies on normal peripheral blood cells, monoclonal antibodies PMN 6 and PMN 29 have previously been shown to react exclusively with neutrophils while AML-2–23 reacts with both neutrophils and monocytes. The present report demonstrates that these antigens are absent from blast cells of patients with acute myelocytic leukemia (AML) classified as M1 and M2 in the French-American-British system and chronic myelocytic leukemia in myeloid blast crisis. However, leukemia cells with myelomonocytic morphology (M4) expressed all three antigens, while cells with pure monocytic features (M5) were generally only positive for AML-2–23. Based on the absence of these antigens on both leukemic and normal myeloblasts and granulocyte-monocyte progenitors and their characteristic patterns of display on more differentiated leukemic and normal cells, we propose a modified concept of normal myelopoiesis. In this hypothesis, the myeloblast is an uncommitted cell that gives rise to a series of intermediate precursors that acquire committment to either the granulocytic or monocytic lineage marked by the acquisition of specific cell surface markers.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 4
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    The expression and modulation of human myeloid-specific antigens during differentiation of the HL-60 cell line (1983)
    American Society of Hematology
    Details
    Publication Date: 1983-06-01
    Description: Antigenic changes detected by myeloid-specific monoclonal antibodies on HL-60 cells induced to differentiate by various chemical mediators were investigated using flow cytometry. Antigen levels detected by monocyte- granulocyte-specific monoclonal antibodies AML-2–23, 61D3, and 63D3 increased dramatically after differentiation of HL-60 cells along the granulocytic pathway by the addition of dimethyl formamide (DMF), dimethylsulfoxide (DMSO), or cis-retinoic acid. The expression of these same antigens also increased in conjunction with monocytoid differentiation when HL-60 cells were treated with supernatants from leukocytes stimulated with phytohemagglutinin (PHA-LCM) or with mixed lymphocyte conditioned medium (MLC). In contrast, treatment of HL-60 cells with phorbol 12-myristate 13-acetate (PMA), which also induced differentiation along the monocyte pathway, had no effect on the expression of these monocyte-associated antigens. The expression of antigens on HL-60 cells recognized by the granulocyte-specified monoclonal antibodies PMN 6 and PMN 29 decreased after treatment of HL- 60 cells with PMA, but remained constant after treatment with DMF, DMSO, cis-retinoic acid, PHA-LCM, or MLC. These results suggest that normal myeloid differentiation may be dependent on various signals and that morphological and cell surface marker maturity may, under some conditions, be separable. The utility of the HL-60 cell line as a model of myeloid differentiation and for evaluation of inductive signals is discussed.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 5
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    The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells (1985)
    American Society of Hematology
    Details
    Publication Date: 1985-04-01
    Description: Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 6
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    Unknown
    The expression of myeloid-specific antigens on myeloid leukemia cells: correlations with leukemia subclasses and implications for normal myeloid differentiation (1983)
    American Society of Hematology
    Details
    Publication Date: 1983-03-01
    Description: The expression of three distinct myeloid-specific cell surface antigens detected by monoclonal antibodies (PMN 6, PMN 29, and AML-2–23) on acute and chronic myeloid leukemia cells is correlated with blast cell morphology and normal myeloid cell antigen display. In studies on normal peripheral blood cells, monoclonal antibodies PMN 6 and PMN 29 have previously been shown to react exclusively with neutrophils while AML-2–23 reacts with both neutrophils and monocytes. The present report demonstrates that these antigens are absent from blast cells of patients with acute myelocytic leukemia (AML) classified as M1 and M2 in the French-American-British system and chronic myelocytic leukemia in myeloid blast crisis. However, leukemia cells with myelomonocytic morphology (M4) expressed all three antigens, while cells with pure monocytic features (M5) were generally only positive for AML-2–23. Based on the absence of these antigens on both leukemic and normal myeloblasts and granulocyte-monocyte progenitors and their characteristic patterns of display on more differentiated leukemic and normal cells, we propose a modified concept of normal myelopoiesis. In this hypothesis, the myeloblast is an uncommitted cell that gives rise to a series of intermediate precursors that acquire committment to either the granulocytic or monocytic lineage marked by the acquisition of specific cell surface markers.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
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  • 7
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    Unknown
    The expression and modulation of human myeloid-specific antigens during differentiation of the HL-60 cell line (1983)
    American Society of Hematology
    Details
    Publication Date: 1983-06-01
    Description: Antigenic changes detected by myeloid-specific monoclonal antibodies on HL-60 cells induced to differentiate by various chemical mediators were investigated using flow cytometry. Antigen levels detected by monocyte- granulocyte-specific monoclonal antibodies AML-2–23, 61D3, and 63D3 increased dramatically after differentiation of HL-60 cells along the granulocytic pathway by the addition of dimethyl formamide (DMF), dimethylsulfoxide (DMSO), or cis-retinoic acid. The expression of these same antigens also increased in conjunction with monocytoid differentiation when HL-60 cells were treated with supernatants from leukocytes stimulated with phytohemagglutinin (PHA-LCM) or with mixed lymphocyte conditioned medium (MLC). In contrast, treatment of HL-60 cells with phorbol 12-myristate 13-acetate (PMA), which also induced differentiation along the monocyte pathway, had no effect on the expression of these monocyte-associated antigens. The expression of antigens on HL-60 cells recognized by the granulocyte-specified monoclonal antibodies PMN 6 and PMN 29 decreased after treatment of HL- 60 cells with PMA, but remained constant after treatment with DMF, DMSO, cis-retinoic acid, PHA-LCM, or MLC. These results suggest that normal myeloid differentiation may be dependent on various signals and that morphological and cell surface marker maturity may, under some conditions, be separable. The utility of the HL-60 cell line as a model of myeloid differentiation and for evaluation of inductive signals is discussed.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
    Location Call Number Expected Availability
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    PAPER CURRENT
  • 8
    facet.materialart.
    Unknown
    The effects of recombinant-DNA-derived interferons on the growth of myeloid progenitor cells (1985)
    American Society of Hematology
    Details
    Publication Date: 1985-04-01
    Description: Interferons (IFNs) have been shown to have significant effects on hematopoietic cell growth. Previous studies defining these effects have utilized mouse and human alpha-, beta-, and gamma-IFN isolated from supernatants of stimulated cells. Despite purification, the possible presence of other lymphokines and soluble factors remains a concern. In this study, the effects of gene-cloned alpha- and gamma-IFN on colony- forming units of granulocyte/macrophage (CFU-GM) progenitors cultured from the peripheral blood of normal volunteers were examined. In addition, blast cell colonies from one patient with acute myelogenous leukemia (AML) were studied. The growth of normal CFU-GM and AML blast cell colonies was inhibited in a dose-dependent manner by gamma- and alpha-IFN. gamma-IFN was ten to 100 times more potent than alpha-IFN in that this species of IFN reduced colony formation by greater than 50% at concentrations of less than 15 antiviral U/mL. The effects of gamma- IFN were neutralized by a monoclonal antibody specific for gamma-IFN. These in vitro studies indicate that human gamma-IFN may be an important modulator of myelopoiesis. Although these data indicate a possible efficacy of gamma-IFN in the treatment of AML, the in vitro results should be considered for their in vivo significance.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
    Location Call Number Expected Availability
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    PAPER CURRENT
  • 9
    facet.materialart.
    Unknown
    Differentiation of a human monocytic cell line by 1,25-dihydroxyvitamin D3 (calcitriol): a morphologic, phenotypic, and functional analysis (1984)
    American Society of Hematology
    Details
    Publication Date: 1984-11-01
    Description: Several recent studies have suggested a role for 1,25-dihydroxyvitamin D3 (calcitriol) in myeloid differentiation. We have examined the effects of calcitriol on the U937 monoblast cell line and found that calcitriol, at near physiologic concentrations, is a potent inhibitor of U937 growth. Moreover, calcitriol induces differentiation to a monocyte-macrophage phenotype marked by enhanced alpha-naphthyl esterase staining. Morphologic changes were attended by de novo induction of the myeloid specific antigen detected by the monoclonal antibody AML-2–23, as well as dramatic increases in Fc receptors for IgG. In addition, calcitriol induced U937 cells to perform phagocytosis and antibody-dependent cellular cytotoxicity. These results indicate the potential activity of calcitriol in myeloid differentiation and additionally suggest a role for calcitriol in monocyte-macrophage activation.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology
    Location Call Number Expected Availability
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    PAPER CURRENT
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