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

We have established an Ag-specific in vitro system for studying the roles of Ag and IL-5 in B cell differentiation and Ig production. The murine B cell leukemia, BCL1B1, was transfected with mu and kappa genomic sequences and VS107 V regions that conferred a T15 Id and phosphocholine-binding specificity upon the cells. Transfected cells were treated with both the T-dependent Ag phosphorylcholine-key-hole limpet hemocyanin (PC-KLH), and 0.5 ng/ml purified IL-5. After 3.5 days steady state mu-mRNA levels increased three- to fourfold over mu-mRNA levels obtained from untreated cultures, or cultures treated with IL-5 or PC-KLH alone. IL-5 alone caused increased Ig secretion and a nearly twofold increase in proliferation. Additionally, cells treated with PC-KLH alone were able to process the Ag and present it to T cells as shown by subsequent lymphokine production. Thus, both Ag and IL-5 used singly appear to interact with their respective receptors, although neither Ag nor IL-5 increased mu-mRNA levels when used singly. The production of increased mu-mRNA levels obtained with Ag plus IL-5 required polymerase II transcription, suggesting that they may act to increase Ig transcription directly.
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PMID:Induction of immunoglobulin mu mRNA in a B cell transfectant stimulated with interleukin-5 and a T-dependent antigen. 248 Mar 80

Two types of activation Ag, low affinity FcR for IgE (Fc epsilon R2)/CD23 and IL-2R (Tac/p55), were expressed and differently regulated on human eosinophilic leukemia cell lines (EoL-1 and EoL-3). Because the binding of IgE on EoL-3 cells was completely inhibited by H107 (anti-Fc epsilon R2/CD23 mAb) but not by irrelevant mAb, essentially all the low affinity Fc epsilon R2 on EoL-3 seemed to be the Fc epsilon R2/CD23 molecules. Both IL-4 and IFN-gamma enhanced the surface expression of Fc epsilon R2, whereas IL-1, IL-2, and IL-5 showed no effects, as determined by surface staining with anti-Fc epsilon R2 antibody (H107). In contrast to Fc epsilon R2 up-regulation, IL-4 and IFN-gamma showed a differential effect on the regulation of IL-2R (Tac/p55). Whereas IFN-gamma up-regulated the receptor expression of IL-2R/Tac, IL-4 did not. The result suggests that these lymphokines are involved in the different aspects of the activation pathway of the eosinophils. The possible role of Fc epsilon R2 and IL-2R on the function of eosinophils in allergic reaction is discussed.
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PMID:Differential regulation of the low affinity Fc receptor for IgE (Fc epsilon R2/CD23) and the IL-2 receptor (Tac/p55) on eosinophilic leukemia cell line (EoL-1 and EoL-3). 252 45

A large scale production of human recombinant IL-5 (hIL-5) was performed by way of recombinant DNA technology. In this study, we transfected Chinese hamster ovary cells with pdKCR-hIL-5gene-dhfr plasmid and selected a cell line, with the use of methotrexate, producing large amounts of hIL-5. The recombinant hIL-5 thus obtained induced IgM production of murine B cell leukemia BCL1, and its activity was inhibited by TB13 anti-mouse IL-5 monoclonal antibody. hIL-5 could be purified from the cell-free supernatants of the transfectants with high recoveries by using anti-mouse IL-5 antibody-coupled immunoaffinity column in combination with a gel permeation column chromatography. N terminal amino acid sequence analysis of purified hIL-5 revealed that a single amino-terminal amino acid (isoleucine) is detected and hIL-5 consists of 115 amino acid residues.
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PMID:Rapid methods for purification of human recombinant interleukin-5 (IL-5) using the anti-murine IL-5 antibody-coupled immunoaffinity column. 260 55

In order to delineate the humoral regulation of eosinophil production, we studied the effects of interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-5 (IL-5), and their combinations on eosinophil colony formation in clonal cell culture. We plated 1,000 bone marrow null cells per dish and in some experiments used polyclonal anti-gibbon IL-3 sera and anti-human GM-CSF. IL-3 or GM-CSF independently from each other supported eosinophil colony formation. Although IL-5 supported formation of small eosinophil colonies, the number of colonies were significantly smaller than that supported by GM-CSF or IL-3. Cytological examination of the constituent cells revealed that some of the apparent eosinophil colonies supported by IL-3 and GM-CSF were mixed colonies containing eosinophils and one or more other lineages. In addition, the majority of the eosinophils seen in cultures with IL-3 and/or GM-CSF proved to be early eosinophil precursors including eosinophilic promyelocytes, myelocytes, and meta-myelocytes. IL-5-supported eosinophil colonies were pure eosinophil colonies and contained mostly maturer eosinophils such as band and segmented forms. These observations indicated that the developmental stages of the targets of IL-3 and GM-CSF are earlier than those of IL-5 and that the primary function of IL-5 is to support terminal maturation of eosinophils.
Leukemia 1989 Jan
PMID:Humoral regulation of eosinophilopoiesis in vitro: analysis of the targets of interleukin-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-5. 264 72

PGM-1 is a transplantable leukemia of C3H/HeJ mice growing as a population of undifferentiated blast cells with a predisposition to form subcutaneous tumors and to grow in lymphoid organs. Cell survival and proliferation in vitro are absolutely dependent on stimulation by hemopoietic growth factors, and up to 100% of tumor cells can form colonies of mature granulocytes and/or macrophages in semisolid cultures, the colonies containing no clonogenic cells. Most clonogenic cells in the leukemic population respond to stimulation by multi-colony-stimulating factor (IL-3) or GM-CSF, but some respond also to M-CSF, G-CSF, IL-4, IL-5, or IL-6. In their surface phenotype and proliferative characteristics in vitro, PGM-1 leukemic cells resemble normal granulocyte-macrophage progenitor cells, and the leukemia may be a useful model for human chronic myeloid leukemia.
Leukemia 1989 Nov
PMID:PGM-1: a transplantable murine leukemia of granulocyte-macrophage progenitor cells. 268 46

Patients with chronic myelogenous leukaemia (CML) in untreated chronic phase are deficient in their ability to generate lymphokine-activated killer (LAK) cells from peripheral blood mononuclear cells although they possess essentially normal levels of CD16+ and Leu19+ lymphocytes, which do not seem to be actively suppressed by tumour cells. Attempts to enhance LAK cell generation in these patients are reported here. Combining the lymphokines interleukins-2, with -4 and -5 (IL-2, IL-4, IL-5), was not successful; in fact, IL-4 depressed LAK cell induction in both normal donors and CML patients. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate also failed to enhance cytotoxicity of normal donors or patients, and indomethacin was similarly without effect. The only agent found to enhance LAK cell induction by IL-2 in normal donors was interferon-gamma (but not IFN-alpha) and even this modest effect was not seen with the cells of CML patients. Increasing concentrations of IL-2 and/or culture duration also failed to improve LAK cell generation by patients. The only improvement in LAK cell generation was observed in CML patients treated for one or more months with IFN-alpha, where a steady increase of LAK activity with time after initiation of therapy was noted. These results show that the blockade of LAK cell induction in chronic-phase myelogenous leukemia patients is difficult to lift pharmacologically in vitro but possibly susceptible to biological response modifiers in vivo.
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PMID:Partial correction of defective generation of lymphokine-activated killer cells in patients with chronic myelogenous leukaemia after in vivo treatment with interferon-alpha (Wellferon). 278 1

In this paper we communicate that cells of a selected B-CLL clone (I83), after 2 days of Staphylococcus aureus Cowan strain 1 (SAC) activation, respond to recombinant IL-2 (rIL-2) and a B cell stimulatory factor (BSF-MP6) and act in strong synergism with induction of simultaneous high-rate proliferation and differentiation. None of the factors alone or other lymphokines (IFN-gamma, TNF-alpha, 12 kDa BCGF, IL-1, IL-4, IL-5, IL-6) induced significant DNA synthesis in SAC-activated cells. However, low levels of IgM were produced by cells stimulated by SAC + rIL-2. The SAC activation was followed by an increase in IL-2 receptor (IL-2R; CD25) expression, and the proliferation induced by BSF-MP6 + rIL-2 could be blocked in a dose-dependent manner by alpha-CD25 antibody. Furthermore, flow cytometric cell cycle studies showed that SAC and BSF-MP6 + rIL-2 stimulated cells underwent a complete transition through the cell cycle to become arrested in G1. The induced proliferation by BSF-MP6 + rIL-2 was dependent on serum but independent of the 2.8% of CD4, CD8, CD14, and CD16 positive cells contaminating the I83 cell population. Previously, we reported that I83 cells activated by 12-O-tetradecanoylphorbol-13-acetate (TPA) were induced to differentiation only but that the addition of BSF-MP6 induced DNA synthesis concomitantly with the differentiation. This paper demonstrates that physiological stimuli can induce both high-rate proliferation and differentiation in a B-CLL clone in vitro. It also suggests that the low proliferation and the differentiation block in vivo, characteristic of most B-CLLs, may reflect a subnormal response of B-CLL cells to growth and differentiation factors, or a dysfunction in the factor production by the patients' T cells.
Leukemia 1989 Aug
PMID:Interleukin-2 and a T cell hybridoma (MP6) derived B cell-stimulatory factor act synergistically to induce proliferation and differentiation of human B-chronic lymphocytic leukemia cells. 217 41

Monoclonal populations from 10 cases of phenotypically well-characterized B-chronic lymphocytic leukemia (B-CLL) and from a single case of hairy cell leukemia were assessed for their ability to respond by mitogenic stimulation to a number of agents described as growth-promoting for normal B cells. These included the recombinant factors interleukin-1 (IL1), IL2, IL4, IL5, and gamma-interferon, partially purified B cell growth factor (BCGF), B cell stimulatory factor 2 (BSF2), and a CDw40 antibody to the Bp50 antigen. With only few exceptions, no factor or combination of factors stimulated B-CLL populations directly to DNA synthesis. By marked contrast, the hairy cells were responsive to IL4, BCGF, and the CDw40 antibody. B-CLL cells could become responsive with the inclusion of the phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) as co-stimulant such that half of the populations were now activated by IL4, particularly when BCGF was also present. Populations refractory to IL4 were, nonetheless, still responsive to BCGF. In only three cases was a significant effect seen with IL2. gamma-interferon could be either inhibitory or stimulatory and, in a few cases, modulated specifically the effects of IL4. In contrast to normal B cell activations, neither the CDw40 antibody nor a calcium ionophore synergized with TPA for stimulating the majority of B-CLL populations. BSF2 was stimulatory in the two cases examined while both IL1 and IL5 were ineffective where studied. No simple correlation was observed between the patterns of responsiveness and the expression of a panel of CD markers assayed on cells both freshly isolated and after TPA stimulation. The data demonstrate a functional heterogeneity not disclosed by simple phenotypic analysis and also indicate the range of activities which can impinge on the growth regulation of monoclonal B cell populations.
Leukemia 1988 Mar
PMID:Stimulation of B-chronic lymphocytic leukemia populations by recombinant interleukin-4 and other defined growth-promoting agents. 312 69

The B-cell differentiation-inducing activity of interleukin-1 (IL-1) was compared with that of T-cell replacing factor (TRF)/interleukin-5 (IL-5), which was originally described as a late-acting B-cell differentiation-inducing factor. Human recombinant IL-1 and murine recombinant TRF/IL-5 were used in this study. Purified B cells from non-primed or antigen-primed mice, LPS-stimulated B-cell blasts, and chronic B-cell leukaemia (BCL1) cells were used as the responding B-cell population. Addition of IL-1 to the culture of normal B-cells and sheep red blood cells (SRBC) induced a dose-dependent anti-SRBC IgM response, with maximal response at 100 U/ml, whereas the response induced by TRF/IL-5 was less than that induced by IL-1 and did not reach the maximum even at 100 U/ml. Addition of anti-IL-1 antibody, but not anti-TRF/IL-5 antibody or anti-IL-2 receptor antibody, inhibited IL-1-induced anti-SRBC responses. Depletion of cells adherent to Sephadex beads from splenic B cells showed no significant effect on the magnitude of the total responses. IL-1 could induce little, if any, differentiation in antigen-primed B cells, LPS-stimulated B-cell blasts, or BCL1 cells into antibody-secreting cells, whereas differentiation could be induced by low doses of TRF/IL-5 (1-2 U/ml). Of great interest is that suboptimal doses of IL-1 (10 U/ml) could synergize with TRF in the primary anti-SRBC PFC responses. Kinetic studies revealed that IL-1 acts on B cells for the first 2 days and TRF/IL-5 for the last 3 days in 5-day cultures of B cells. These results suggest that IL-1 acts primarily on resting B cells as a differentiation-inducing factor in the presence of antigen, and also acts as a 'priming' factor for TRF/IL-5.
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PMID:Role of recombinant interleukin-1 compared to recombinant T-cell replacing factor/interleukin-5 in B-cell differentiation. 328 Apr 72

We have previously demonstrated a constitutive expression of transforming growth factor alpha (TGF-alpha) in normal human blood eosinophils, both at the mRNA and protein level. This may indicate a novel function of the eosinophil, the regulation of which has not been clarified. Therefore human white blood cells (WBC) were treated with potential regulators of eosinophil function. Northern blot analysis demonstrated that human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) caused a time and dose-dependent 2- to 3-fold increase of TGF-alpha mRNA levels, in relation to incubation in the absence of cytokine; maximal response was attained within 4 h of incubation. In contrast, IL-5 failed to influence the expression of the TGF-alpha gene. In situ analysis of GM-CSF- or IL-3-stimulated cells showed that eosinophils remained the sole cell type expressing TGF-alpha mRNA. However, whereas GM-CSF significantly induced, within 1 h, release of immunoreactive TGF-alpha protein, IL-3 was insufficient in this respect. In conclusion, our findings indicate that expression of TGF-alpha gene and protein in normal blood eosinophils is differently regulated by GM-CSF and IL-3.
Leukemia 1994 Apr
PMID:Transforming growth factor alpha expression in normal human blood eosinophils: differential regulation by granulocyte-macrophage colony-stimulating factor and interleukin-3. 751 73


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