0000000000181530
AUTHOR
Friedhelm Herrmann
showing 37 related works from this author
Granulocyte-macrophage colony-stimulating factor induces cytokine secretion by human polymorphonuclear leukocytes.
1989
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is known as an inducer of proliferation and functional activation of myeloid cells. This study was carried out to characterize the effects of GM-CSF on polymorphonuclear leukocytes (PMN) more extensively. Using Northern blot analysis, we show that PMN are able to accumulate mRNAs for different cytokines, including tumor necrosis factor-alpha (TNF-alpha); G-CSF, and M-CSF, all of which are involved in inflammation and hematopoiesis. Biological assays and immunoassays demonstrate that PMN translate these mRNAs, except TNF-alpha, into secretory proteins. However, the expression of these cytokines is dependent on stimulation by exogenous…
Identification and purification of human erythroid progenitor cells by monoclonal antibody to the transferrin receptor (T� 67)
1988
Anti-TU 67 is a murine monoclonal antibody that recognizes the transferrin receptor. With respect to hematopoietic cells TU 67 is expressed by human multipotent colony-forming cells (CFU-Mix), erythroid progenitor cells (BFU-E and CFU-E) and a fraction of granulocyte/monocyte colony forming cells, but is not expressed by mature hematopoietic cells including erythrocytes, platelets, lymphocytes, and peripheral blood myeloid cells. The TU 67-positive fraction of normal bone marrow, separated by fluorescence-activated cell sorting (FACS) or immune rosettes, contained 87% of the erythroid progenitor cells. Erythroid progenitor cells were enriched up to 50-fold by using a combination of monoclon…
The suppressive effects of recombinant human tumor necrosis factor‐alpha on normal and malignant myelopoiesis: Synergism with interferon‐gamma
1988
The modulation of growth of normal and leukemic myeloid progenitor cells in soft agar cultures by recombinant human tumor necrosis factor-alpha (TNF alpha) and recombinant human interferon-gamma (IFN gamma) was investigated. TNF alpha inhibited colony formation of all colony types representing different maturational stages of normal progenitor cells committed to the myeloid lineage with different orders of sensitivity. Blast-type colonies derived from patients with acute myelogenous leukemia were more sensitive to TNF alpha inhibition than progenitor cells purified from normal bone marrow or bone marrow from patients with stable-phase chronic myelogenous leukemia. The response of most colon…
A phase-II study of low-dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma.
1989
Recent preclinical and clinical studies that have demonstrated antitumor activity of high-dose recombinant interleukin-2 (rIL-2), and animal models that demonstrated a synergistic effect of low-dose cyclophosphamide, led us to study rIL-2 (Cetus Corp., Emeryville, Calif) in a phase II clinical trial in combination with low-dose cyclophosphamide in 32 patients, 18 with malignant melanoma and 14 with renal cell carcinoma. rIL-2 was given once daily at 3 x 10(6) U/m2, as a 30-min infusion for 14 days in cycle I and for 2 x 5 days in cycles II and III respectively; if tolerated, the dose was increased to a maximum of 6 x 10(6) U m-2 day-1; the cycles, separated by 1 week treatment-free interval…
High-level secretion of tumor necrosis factor-alpha contributes to hematopoietic failure in hairy cell leukemia [see comments]
1989
Hairy cell leukemia (HCL) is frequently associated with severe pancytopenia. The authors detected high levels of tumor necrosis factor (TNF)-alpha in the bone marrow serum of patients with HCL and found anti-TNF-alpha neutralizing monoclonal antibodies (MoAbs) to be able to enhance hematopoiesis of HCL patients in in vitro colony assays. As potent producers of TNF-alpha, hairy cells could be identified, thus implicating the malignant population in the pathogenesis of hematopoietic failure due to inappropriate secretion of this cytokine.
Mechanisms of Autocrine and Paracrine Growth Control in Acute Myelogenous Leukemia
1990
Blast cells of a high proportion of patients with acute myelogenous leukemia (AML) proliferate in response to exogenous hematopoetic growth factors, both in vitro [9, 14, 26, 36, 48, 65] and in vivo [20]. Whereas leukemic colony-forming cells (L-CFCs) from most patients share their growth factor dependence with normal committed myeloid progenitor cells (CFU-GMs), some AML samples autonomously form colonies in agar and are therefore believed to bypass growth factor requirements [17, 42, 72]. Autocrine growth factor production has been identified as one mechanism used by AML blasts to supply various growth-promoting molecules. Moreover nontransformed accessory bone marrow cells have been show…
MACOP-B chemotherapy for the treatment of high grade and intermediate grade non Hodgkin's lymphoma.
1990
Between Nov. 1985 and Nov. 1988, sixty-three patients with high grade malignant (hg) and intermediate grade malignant (img) Non Hodgkin's Lymphoma (NHL) were treated with MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin). Thirty-seven patients received MACOP-B as an upfront treatment modality, whereas twenty-six patients had relapsed disease and received MACOP-B as a salvage protocol. Four weeks after termination of therapy, 75% of patients with de novo NHL and 72% of the patients with relapsed NHL were in complete remission (CR). In the group of newly diagnosed NHL, 22% achieved partial remission (PR) and 3% no change (NC), whereas in the group wi…
Granulocyte-macrophage colony-stimulating factor (CSF) and multilineage CSF recruit human monocytes to express granulocyte CSF
1989
Abstract We assessed the capacity of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and multilineage (Multi)-CSF to induce release of granulocyte-CSF (G-CSF) by highly purified peripheral blood monocyte (Mo) preparations. Our results reveal that GM-CSF and Multi-CSF, either alone or in a synergistic concert, activate Mo to transcribe G-CSF messenger (m) RNA and release biologically active G- CSF protein into their culture supernatants. G-CSF had no regulatory effect on Mo expression of cytoplasmic G-CSF mRNA levels and G-CSF protein secretion by itself. These differential actions of CSFs provide further insight into self-regulatory mechanisms within the growth f…
Incidence of lineage promiscuity in acute myeloblastic leukemia: Diagnostic implications of immunoglobulin and T-cell receptor gene rearrangement ana…
1988
Abstract Sixty-nine blood or bone marrow samples from both children and adults with acute myeloblastic leukemia (AML) were investigated to elucidate the frequency of immunoglobulin (IG) and T-cell receptor (TCR)-gene rearrangements. Non-germline configuration for the IG heavy chain (h) gene was detected in the specimens of nine patients of various subtypes according to the French-American-British classification (FAB), including FAB M1, M2, M4 and M5. Rearrangement of the IG kappa chain (k) gene was present in one of these cases which simultaneously revealed a rearranged TCR-beta (b) chain gene. In another two AML samples we found TCR-b gene rearrangements, in one case in combination with an…
Minimal peripheral blood cells carrying clonal markers of b cell disorders: Evidence for monoclonality of circulating lymphocytes in patients with mu…
1989
Peripheral blood lymphocytes (PBL) of 20 patients with multiple myeloma (MM) were assayed for clonality by Southern blot and cell surface marker analysis. Eight samples showed monoclonal origin of circulating lymphocytes by demonstrating rearrangements of the heavy chain immunoglobulin gene (IgH). In selected experiments, comparison of IgH rearrangements of bone marrow plasma cells and peripheral blood-derived mononuclear cells, highly enriched for B lymphocytes, proved to be identical. However, monoclonal circulating cells could not be detected in samples with rearranged IgH genes by surface marker phenotyping using one-color immunofluorescence analysis and a panel of monoclonal and polycl…
High-level secretion of tumor necrosis factor-alpha contributes to hematopoietic failure in hairy cell leukemia [see comments]
1989
Abstract Hairy cell leukemia (HCL) is frequently associated with severe pancytopenia. The authors detected high levels of tumor necrosis factor (TNF)-alpha in the bone marrow serum of patients with HCL and found anti-TNF-alpha neutralizing monoclonal antibodies (MoAbs) to be able to enhance hematopoiesis of HCL patients in in vitro colony assays. As potent producers of TNF-alpha, hairy cells could be identified, thus implicating the malignant population in the pathogenesis of hematopoietic failure due to inappropriate secretion of this cytokine.
Polypeptides controlling hematopoietic cell development and activation. I. In vitro results.
1989
Recombinant DNA technology has been central in answering some of the most relevant questions in the research of regulation of the functional status of hematopoietic progenitor cells and their progeny. This leading article will focus on recent results that have emerged from studies utilizing recombinant molecules that control hematopoietic blood cell development and activation. The following features will be detailed: The molecular and biological characteristics and biochemistry of hematopoietic growth factors, synergizing factors and releasing factors, their role in the regulation of hematopoiesis and activation of normal and leukemic cells, their cellular sources, and regulation of product…
Monocyte Interleukin-1 Secretion Is Regulated by the Sequential Action of γ-Interferon and Interleukin-2 Involving Monocyte Surface Expression of Int…
1989
Interleukin-1 (IL-1) is a polypeptide synthesized as a high-mol.-wt. precursor and subsequently secreted after proteolytic cleavage to 17500-dalton active forms in murine [1] and human cells [2]. Recently, cDNAs for murine [3] and for two distinct human IL-1 species, IL-1α and IL- 1β, have been isolated, sequenced, and cloned [2, 4].
Recombinant human granulocyte-macrophage colony-stimulating factor induces secretion of autoinhibitory monokines by U-937 cells
1988
Colony-stimulating factors are required for survival proliferation, differentiation and functional activation of granulocytes, macrophages and their precursor cells. In the present report, however, we demonstrate antiproliferative activity of recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) on monoblast cell line U-937 and provide evidence for the involvement of tumor necrosis factor alpha TNF-alpha and interleukin 1 beta (IL 1 beta) in its growth inhibitory action. GM-CSF (but not granulocyte CSF, G-CSF or macrophage CSF, M-CSF) suppressed DNA synthesis and self renewal of U-937 cells. Similarly, medium conditioned by U-937 cells in response to GM-CSF (GM-CS…
Polypeptides controlling hematopoietic blood cell development and activation
1989
Colony-stimulating factors (CSFs) have entered the clinical arena. Several investigators have explored, in first clinical phase I studies, different routes of administration to define the optimum biological dose, maximum tolerated dose, toxicity, and pharmacokinetics of these reagents. It has been demonstrated that recombinant human (rh) granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) can be safely administered over a broad dose range to increase number of circulating granulocytes in man. More recently, GM-CSF and G-CSF have been involved in phase Ib/II studies to assess the granulopoietic responses of patients with granulocytopenia due to various underlying disease states i…
Differential regulation of interleukin-6 expression in human fibroblasts by tumor necrosis factor-alpha and lymphotoxin.
1990
The treatment of human diploid fibroblasts with tumor necrosis factor (TNF)-alpha and with lymphotoxin (LT) is associated with induction of interleukin-6 (IL-6) transcripts with TNF-alpha being 10-fold more potent than LT. Here we report on the TNF-alpha/LT-induced signaling mechanisms responsible for the regulation of IL-6 gene expression in these cells. Run-on assays demonstrated that both TNF-alpha and LT increase IL-6 mRNA levels by transcriptional activation of this gene. Stability studies of IL-6 transcripts in fibroblasts showed that TNF-alpha delayed IL-6 mRNA decay but not LT. The induction of IL-6 transcripts by TNF-alpha and LT was not inhibited by the isoquinoline sulfonamide de…
Hematopoietic responses in patients with advanced malignancy treated with recombinant human granulocyte-macrophage colony-stimulating factor.
1989
The in vivo effect of yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) was investigated in 30 patients with advanced malignancy in a phase Ib trial. Patients were treated at four different dose levels (120 to 1,000 micrograms/m2/d) by either daily intravenous (IV) bolus injection or 24-hour continuous infusion. Administration of rh GM-CSF resulted in a broad spectrum of dose- and schedule-dependent hematopoietic effects. Sustained infusion of rh GM-CSF elicited a maximum 17-fold average peak increase of the total WBC count with mainly neutrophils, eosinophils, and monocytes accounting for this rise, and increases in bone marrow cellularity with a…
Interleukin 1 stimulates T lymphocytes to produce granulocyte-monocyte colony-stimulating factor.
1988
T lymphocytes are thought to cooperatively interact with monocytes to produce colony-stimulating factors (CSF). However, little is known about monocyte-mediated signals leading to CSF-secretion by T lymphocytes, although soluble monocyte products have been implicated. We have employed monoclonal antibody anti-T3B covalently coupled to CnBr-activated Sepharose 4B beads, to show that multimeric ligation of T cell antigen receptor leads to T cell receptiveness to interleukin 1 (IL-1), as indicated by T cell production of CSF, which induces growth of myeloid progenitor cells into neutrophil, eosinophil, and monocyte colonies. To investigate the molecular basis of these findings, total RNA was e…
Gamma-Interferon Regulates Secretion of G-CSF in Human Monocytes on the Transcriptional Level
1987
The production of colony stimulating factors (CSF) for granulocytes and monocytes is integrated into a network of communicating soluble messenger molecules resulting from T-cell/monocyte interactions. We assessed the capactiy of gamma-Interferon to modulate monocyte secretion of CSF by colony assays and Northern blot analysis to hybridize monocyte RNA with cDNA probes of different CSF-types. Whereas mRNA for GM-CSF was undetectable in untreated and gamma-IFN treated peripheral blood monocytes, the constitutive expression of mRNA for G-CSF and subsequent production of a CSF with biological activities similar to G-CSF could highly be enhanced by exposure of monocytes to gamma-IFN.
Cytokines with Possible Clinical Utility
1987
Biological response modifiers (BRM) are agents aimed at reducing tumor growth, not primarily by exerting direct cytotoxic effects but by modulation of tumor gene expression (e.g., induction of differentiation) or by enhancing host defense mechanisms directed against cancer cells. BRM as primary therapy or as adjuncts to cytotoxic agents in the treatment of cancers have attracted increasing interest in view of stagnating clinical results in many areas [1], and there is increasing evidence of in vitro and in vivo efficacy of these agents. Furthermore, advances in molecular biology suggesting that oncogenes and their products play a crucial role in oncogenesis support approaches to modulation …
Abnormal Marker Expression in Acute Leukemia (AL) Characterized by Monoclonal Antibodies and Flow Cytometry
1987
The application of refined immunologic and enzymatic markers to conventional morphologic and cytochemical techniques has revealed an unexpected heterogeneitiy in acute leukemia (AL). Since the development of monoclonal antibodies (MoAbs) to lineage specific differentiation markers, there have been several reports of AL patients whose blast cells represent relatively homogeneous populations with phenotypic features of more than one cell line [1–5] or are characterized by the coexistence of separate cell populations each demonstrating either lymphoid or myeloid features [6–10].
Leukemic Colony-Forming Cells in Acute Myeloblastic Leukemia: Maturation Hierarchy and Growth Conditions
1987
Despite their primitive morphological appearance, the majority of leukemic blasts in acute myeloblastic leukemia (AML) are end-stage, nonproliferating cells. Only a small subset of AML blasts are capable of a sufficient number of divisions to form colonies in semisolid medium [1, 2]. It has been suggested that these leukemic colony-forming cells (L-CFC) may act in vivo as progenitor cells to maintain the rest of the leukemic cell population [3, 4]. L-CFC share several properties with normal myeloid progenitor cells, including self-renewal potential and high thymidine suicide index [2, 3]. As in the case of normal myeloid progenitor cells (NMPC), colony growth of L-CFC from most patients req…
Tumor necrosis factor (TNF)-alpha but not TNF-beta induces secretion of colony stimulating factor for macrophages (CSF-1) by human monocytes
1987
Abstract Tumor necrosis factor (TNF)-alpha has been identified as a major inducer of colony stimulating factor (CSF)-secretion by human vascular endothelial cells and fibroblasts. In the present study we assessed the capacity of TNFs to induce release of CSF-1 from highly purified peripheral blood monocyte preparations. Whereas monocytes do not accumulate CSF-1 messenger (m)RNA constitutively and consequently do not produce CSF-1 protein, CSF-1 mRNA and protein secretion became detectable, when monocytes were cultured in the presence of TNF-alpha, that was synergistically enhanced by interferon-gamma (IFN-gamma). However, under identical experimental conditions TNF-beta failed to induce mon…
Hematopoietins: New Tools in the Treatment of Hematopoietic Insufficiency
1993
The number of circulating blood cells and their function are regulated by a variety of peptide hormones, the so-called hematopoietic growth factors (HGFs) or hematopoietins. In a complex regulatory network of stimulating and inhibiting peptide hormones [1], the number of circulating blood cells is kept at a physiological level. Because many of these blood cells have a relatively short half-life, the bone marrow is in a state of constant active proliferation in order to produce the necessary blood cells. For instance, granulocytes are made at a rate of 5 × 107–10 × 107 cells/s. It is unclear whether additional, hematopoietin-independent regulatory mechanisms exist, which might be responsible…
Production of macrophage-, granulocyte-, granulocyte-macrophage- and multi-colony-stimulating factor by peripheral blood cells
1989
The specific cell sources and signals for induction of various colony-stimulating factors (CSF) in peripheral blood mononuclear cells (PBMC), purified T lymphocyte and monocyte (Mo) populations have been investigated. In the absence of exogenous activating stimuli, human PBMC, T cells and Mo failed to produce stable cytoplasmic mRNA for CSF for macrophages (M-CSF or CSF-1), for granulocytes (G-CSF), for granulocytes and macrophages (GM-CSF) and for multilineage CSF [multi-CSF, interleukin (IL) 3] and thus failed to release CSF proteins. However, after stimulation with phorbol myristate acetate and phytohemagglutinin, M-, G-, GM- and multi-CSF mRNA became detectable in PBMC, resulting in the…
Effect of Granulocyte-Macrophage Colony-Stimulating Factor on Neutropenia and Related Morbidity Induced by Myelotoxic Chemotherapy
1990
Myelosuppression-related neutropenia is the major side effect of most anticancer chemotherapy. Despite considerable improvements in supportive care due to the advent of a variety of new antibiotic combinations, infection remains the main risk arising during the neutropenic period that follows intensive chemotherapy for cancer [1]. In addition, neutropenia is the major obstacle to dose escalation, frequency of cytoreductive treatment, and thus to improved cancer control. Regarding reduction of the period of neutropenia and increase of the maximum tolerated dose of effective anticancer agents, autologous bone marrow transplantation (ABMT) has recently offered new promise. However, as many as …
Interferon alfa-2c in chronic myelogenous leukemia (CML): hematologic, cytogenetic and molecular-genetic response of patients with chronic phase CML …
1990
Alpha- and gamma-interferons have been shown to actively suppress hematopoiesis in patients in the chronic phase of chronic myelogenous leukemia in vitro and in vivo. Since both interferons act through different receptors on their hematopoietic target cells, they are expected to be capable of independently inhibiting abnormal blood cell development in patients with chronic myelogenous leukemia. We have utilized recombinant human interferon alfa-2c to treate 11 patients with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase, who were resistant to previous interferon gamma therapy. Ten of the patients were evaluable for hematologic, cytogenetic and molecular-genet…
Effect of granulocyte-macrophage colony-stimulating factor on neutropenia and related morbidity induced by myelotoxic chemotherapy.
1990
Abstract purpose: A phase Ib/II clinical study was undertaken to assess the efficacy of recombinant human (rh) granulocyte-macrophage colony-stimulating (GM-CSF) factor in attenuating neutropenia and associated morbidity caused by high-dose anticancer chemotherapy administered in the presence or absence of autologous bone marrow support. patients and methods: Twenty-two patients with various solid tumors and lymphoid neoplasias were treated with a single daily subcutaneous dose of rh GM-CSF (250/μg/m 2 ) 48 hours after receiving a second cycle of highly myelotoxic chemotherapy for a period of 10 days. Within-subject comparisons on neutropenia-related clinical and laboratory variables were m…
Cytokines in cancer therapy
1989
The treatment options for patients with cancer are presently limited to surgical and radiotherapeutic strategies for localized disease and the systemic use of cytotoxic drugs for disseminated disease. So far, chemotherapy remains the mainstay for the treatment of metastatic cancer. Treatment results, however, have been stagnant particularly for the more frequent cancers such as lung cancer, breast cancer and colorectal cancer. Current research is seeking new concepts of cancer treatment, based upon a more profound understanding of tumor cell biology. The oncogenetic defect in neoplastic cells is a genetic alteration in a primordial cancer cell, which subsequently leads to clonal expansion a…
Acute Nonlymphocytic Leukemia in Adults: Pathophysiology, Status of Current Therapy, and New Approaches
1987
Recent information concerning the cell biology of leukemias has provided new insights into the pathophysiology and pathogenesis of acute leukemia, involving the detection of leukemia viruses, oncogenes and their products, and the discovery of factors supporting clonal leukemic growth. Murine, avian, and cat leukemia viruses are well characterized. To date, only HTLV I appears to be a likely candidate as a human leukemia virus. For both avian and murine viruses, there is a fundamental classification distinction between long-latency viruses (LLV) and acute transforming viruses (ATV). The ATV are replication defective and must be propagated with a helper virus. They have within their genome an…
Lymphokine activated killer cells.
1989
Various subpopulations of human leukocytes may be induced by lymphokines to exert cytotoxic activity. In man major histocompatibility complex non-restricted tumor cell lysis by interleukin-2 (IL-2) induced peripheral blood lymphocytes is attributed mainly to natural killer cells. These T cell receptor negative large granular lymphocytes are called lymphokine activated killer (LAK) cells. In order to explore the potential of LAK cells in tumor therapy, several clinical studies have been conducted, using IL-2 alone or in combination with ex vivo IL-2-activated peripheral blood lymphocytes. Objective responses have reproducibly been achieved only in renal cell carcinoma and malignant melanoma …
Effect of Treatment with rhGM-CSF and Low-Dose Cytosine Arabinoside on Leukemic Blast Cells in Patients with Myelodysplastic Syndromes
1990
Treatment of patients having myelodysplastic a syndromes (MDS) with approaches such as differentiation induction, single cytostatic agents or supportive care only has, up to now, been rather unsuccessful. Aggressive chemotherapy followed by bone marrow transplantation is only suitable for a very small proportion of patients. Thus, there is a need for new therapeutic alternatives.
Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy.
1989
Abstract The effect of recombinant human granulocyte colony-stimulating factor (G-CSF) on hematologic parameters was evaluated in a phase I clinical study in 18 patients with advanced malignancy. G-CSF was administered once daily as a 30-minute infusion for 14 days; three patients each were treated at increasing dose levels of 1, 3, 10, 30, and 60 micrograms kg-1 day-1. A transient decrease in neutrophil and monocyte counts was observed immediately after the G-CSF infusion, followed by a dose-dependent increase of up to 15-fold. G-CSF-induced neutrophils exhibited an increased O2- radical production, and serum levels of enzymes related to granulocyte turnover, including lysozyme and elastas…
Surface Marker Analysis by Monoclonal Antibodies: A Valuable Technique in Childhood Acute Myeloid Leukemia
1987
A considerable number of monoclonal antibodies (MoAbs) with myeloid activity have been described during the last few years (summarized in [1]). These MoAbs have been applied to the study of normal myeloid differentiation, as well as to the surface marker analysis of acute myeloid leukemia (AML) [2–6]. Although there is a strong tendency for morphological differentiation to correspond to surface antigen differentiation of malignant myeloid cells [2, 3], a recent report has failed to correlate the FAB classification system with immunologic categories of AML [6].
Phase I trial of recombinant human tumour necrosis factor alpha in patients with advanced malignancy.
1991
A phase I clinical trial was conducted with recombinant human tumour necrosis factor alpha (rhTNF-alpha) in 62 patients with advanced malignancy refractory to previous standard therapy. rhTNF-alpha was given as a 30 min infusion twice a day at 6 h intervals. A total of 10 different dose levels was escalated in cohorts of 6 patients ranging from 2.5 to 200 micrograms/m2 twice a day for 5 days every second week for a total of 8 weeks followed by a 4-week observation period. Major side-effects of TNF-alpha therapy, seen in almost all patients studied, were fever and chills. As dose-limiting side-effects hypotension and liver toxicity were recorded in 4 of 5 patients treated with 200 micrograms…
Interleukin-4 induces secretion of CSF for granulocytes and CSF for macrophages by peripheral blood monocytes.
1989
Abstract T cells are known to interact cooperatively with monocytes to produce Colony-Stimulating Factors (CSF), although T cell-mediated signals leading to CSF secretion by monocytes are not completely understood. We have made use of Northern blot hybridization and specific bioassays to study the effects of the T cell product interleukin-4 (IL-4) on monocyte CSF expression. The results suggest a previously unrecognized role of IL-4 as a CSF inducer since exposure of monocytes to IL-4 resulted in accumulation of transcripts for granulocyte-CSF (G-CSF) and macrophage-CSF (M-CSF). Consequently, IL-4-activated monocytes released factors in their culture supernatants biologically and antigenica…
Role of colony‐stimulating factors in the biology of acute myelogenous leukemia
1989
A high proportion of acute myeloid leukemias (AML) recently investigated for their capacity to synthesize biologically active bioregulatory molecules was found to accumulate messenger (m) RNA and to produce membrane-bound or -secreted forms of stimulating factors for granulocyte, macrophage and mixed granulocyte-macrophage colony growth. Blast cells have also been found to secrete interleukin 1, tumor necrosis factor-alpha, interleukin 6, and to express receptors for various growth factors as well. However, growth factors like interleukin 2 and interleukin 3 have not been identified as AML products, and several other factors including interleukin 4, interleukin 5, etc. need further evaluati…