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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.
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PMID:Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment. 152 Aug 88

Fc receptors (FcR) are of importance in immune and inflammatory reactions. FcR expression as mRNA and surface protein was therefore examined in the myelomonocytic cell line, U937, after stimulation with phorbol ester (PMA), in the presence of seven different cytokines (interferon-gamma [IFN gamma], IFN alpha, granulocyte-macrophage colony-stimulating factor [GM-CSF], tumour necrosis factor-alpha [TNF alpha], TNF beta, interleukin-beta [IL-1 beta], IL-2) or dexamethasone. HLA class I and CD11b expression were also examined. Cell surface expression of FcRI and II was measured by flow cytometry using monoclonal antibodies, and the mRNA of FcRII was measured with cDNA or oligonucleotide probes. The major findings were: PMA increased cell surface FcRI, FcRII and CD11b, but decreased HLA; PMA caused a fivefold increase in all three FcRII RNA transcripts (2.5, 1.5 and 0.9 kb) in Northern analysis; IFN gamma, IFN alpha and GM-CSF increased the expression of FcRI and II, and there was no effect with IL-1 beta, IL-2, TNF alpha or TNF beta (only GM-CSF increased the expression of CD11b); all cytokines further increased FcRI and FcRII expression in the presence of PMA; HLA expression was also increased in the presence of PMA, IFN alpha and IFN gamma; dexamethasone reduced the levels of FcRI and II in cells stimulated with PMA with or without cytokines. Thus stimulatory agents and cytokines can alter the expression of surface Fc gamma R and mRNA encoding FcRI or II, providing potential control mechanisms for the modulation of these receptors in inflammatory responses.
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PMID:Effects of PMA, cytokines and dexamethasone on the expression of cell surface Fc receptors and mRNA in U937 cells. 135 19

The ability of circulating mononuclear cells from recipients of HLA identical sibling marrow transplants to generate messenger (m) RNA for the haemopoietic growth factors interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) upon mitogen stimulation was investigated. The amount of IL-3 mRNA per ml of blood and IL-3 mRNA per 10(7) mononuclear cells as well as the amount of GM-CSF mRNA per ml of blood was significantly lower in transplant recipients than in normal volunteers. Lower values for mRNA expression for both IL-3 and GM-CSF were associated with the use of immunosuppressive therapy post transplant. No correlation was found between the expression of message for either cytokine, or the presence or absence of acute graft-versus-host disease at the time of testing. While there was no correlation between the quantity of GM-CSF message produced and time elapsed post transplant, IL-3 message expression increased slightly with increasing time post transplant. These defects of haemopoietic regulators constitute another parameter of impaired cellular immunity occurring after allogeneic marrow transplantation.
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PMID:Cytokine activity after allogeneic bone marrow transplantation. IV. Production of mRNA for IL-3 and GM-CSF by mitogen-stimulated circulating mononuclear cells. 151 Dec 55

In a prospective randomized study, five European transplant centers compared recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; mammalian glycosylated) with placebo. rhGM-CSF was administered in a dose of 8 micrograms glycoprotein (5.5 micrograms protein)/kg/d, as a continuous intravenous (IV) infusion for 14 days, starting 3 hours after bone marrow infusion. Fifty-seven patients entered and completed the study. Median age of the recipients was 34 years (range, 17 to 51 y). All donors were HLA-identical, MLC-nonreactive siblings. Marrow grafts were depleted of T lymphocytes either by counterflow centrifugation (n = 42) or by immunological methods (n = 15). Twenty-nine patients received rhGM-CSF and 28 patients placebo. The leukocyte count and the absolute neutrophil count were significantly higher in the rhGM-CSF-treated group from day +9 to day +14 after bone marrow transplantation (BMT). This was also true for the monocyte count from day +12 to day +21. Early neutrophil (greater than 0.1 and greater than 0.3 x 10(9)/L) and early leukocyte (greater than 0.3 and greater than 0.5 x 10(9)/L) recovery was significantly faster for the patients given GM-CSF. The incidences of graft-versus-host disease (GVHD) and transplant-related mortality were not different in both groups. However, the number of bronchopneumonias was significantly lower in the rhGM-CSF-treated group (P = .03). Long-term follow-up showed a trend to better overall disease-free survival at 2 years and a trend to a lower relapse risk in patients treated with rhGM-CSF. This study shows that rhGM-CSF significantly increases neutrophil and monocyte counts during periods of 6 to 10 days in the second and third week after BMT. This shortened period until myeloid cell recovery after transplantation resulted in a decreased number of pneumonias, without an increase in incidence of GVHD or relapse.
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PMID:Recombinant human granulocyte-macrophage colony-stimulating factor accelerates neutrophil and monocyte recovery after allogeneic T-cell-depleted bone marrow transplantation. 153 59

This study was undertaken in an effort to understand the role of cytokines in T lymphocyte trafficking into inflamed synovium and in the potential enhancement of antigen presentation by human synovial fibroblasts. We found that interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interferon-gamma (IFN gamma) each increased the cell surface expression of intercellular adhesion molecule 1 (ICAM-1) on human synovial fibroblasts in a dose- and time-dependent manner. Maximal ICAM-1 expression occurred within 8 hours of induction, with the following order of efficacy: IFN gamma greater than TNF alpha greater than IL-1 beta. The number of cells bearing the ICAM-1 antigen also increased, from a basal level of approximately 30% to more than 83% after cytokine induction (for all 3 cytokines). ICAM-1 expression rapidly decreased following cytokine removal. The expression of lymphocyte function-associated antigen 3 was also examined, but it was not changed by any of the 3 cytokines. Class I major histocompatibility complex antigen expression was increased modestly by all 3 cytokines, and expression was maximal by 24 hours after treatment. Only IFN gamma induced HLA class II antigen expression, and this expression persisted for up to 6 days following removal of the lymphokine. IL-6 and granulocyte-macrophage colony-stimulating factor had no effect on any of the parameters examined. Our data support an interactive role for inflammatory cytokines and the expression of adhesion ligands and HLA antigens by human synovial fibroblasts in the pathogenesis of synovial inflammation in rheumatoid arthritis.
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PMID:Role of cytokines in inflammatory synovitis. The coordinate regulation of intercellular adhesion molecule 1 and HLA class I and class II antigens in rheumatoid synovial fibroblasts. 170 92

We investigated the in vitro hematopoietic stimulatory activity of leukemia inhibitory factor/human interleukin for DA cells (LIF/HILDA) on bone marrow progenitor populations in 17 normal individuals. In serum-free cultures LIF/HILDA did not induce colony growth. In serum containing media, LIF/HILDA stimulated the growth of colony forming unit (CFU)-MIX and CFU-EO in a dose-dependent fashion and resulted in an increased CFU-MIX and burst forming unit-erythrocytes (BFU-E) colony size. Similar stimulatory effects were seen on a highly purified hematopoietic progenitor population obtained after immunomagnetic depletion of mature myeloid precursors and lymphoid cells. Addition of LIF/HILDA to cultures containing maximally stimulatory concentrations of recombinant human interleukin-3 (rhuIL3), rhuIL3 + rhuIL6, or rhu granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) in serum containing media significantly increased the number of CFU-MIX and eosinophil colonies and increased size and cluster number of CFU-MIX and BFU-E. Depletion of accessory T lymphocytes or monocytes from bone marrow progenitors did not alter the response of hematopoietic precursors to LIF/HILDA. A similar increased colony growth was seen when LIF/HILDA was added to cultures of positively selected CD34/HLA-DR+ or CD34+/HLA-DR- bone marrow hematopoietic progenitor cells stimulated with maximally stimulatory concentrations of rhuIL3 + rhuIL6. LIF/HILDA is a novel cytokine capable of stimulating growth and proliferation of multi-lineage, erythroid, and eosinophil colonies in the presence of serum. LIF/HILDA exerts its activity by direct interaction with highly purified immature bone marrow progenitor cells, has an additive effect when used with other cytokines known to stimulate primitive hematopoietic precursors, and does not require accessory cells.
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PMID:Leukemia inhibitory factor/human interleukin for DA cells: a growth factor that stimulates the in vitro development of multipotential human hematopoietic progenitors. 170 32

Purified natural (n) and recombinant (r) murine (mu) mast cell growth factor (MGF, a c-kit ligand) were evaluated alone and in combination with r human (hu) erythropoietin (Epo), rhu granulocyte-macrophage colony-stimulating factor (rhuGM-CSF), rhuG-CSF, and/or rhuM-CSF for effects in vitro on colony formation by multipotential (colony-forming unit-granulocyte, erythroid, monocyte, megakaryocyte [CFU-GEMM]), erythroid (burst-forming unit erythroid [BFU-E]) and granulocyte-macrophage (CFU-GM) progenitor cells from normal human bone marrow. MGF was a potent enhancing cytokine for Epo-dependent CFU-GEMM and BFU-E colony formation, stimulating more colonies and of a larger size than either rhu interleukin-3 (rhuIL-3) or rhuGM-CSF. MGF, especially at lower concentrations, also acted with rhuIL-3 or rhuGM-CSF to enhance Epo-dependent CFU-GEMM and BFU-E colony formation. MGF had little stimulating activity for CFU-GM colonies by itself, but in combination with suboptimal to optimal amounts of rhuGM-CSF enhanced the numbers and the size of CFU-GM colonies in an additive to greater than additive manner. While we did not detect an effect of MGF on CFU-G colony numbers stimulated by maximal concentrations of rhuG-CSF, MGF did enhance the size of CFU-G-derived colonies. MGF did not enhance the activity of rhuM-CSF. In a comparative assay, maximal concentrations of rmu and rhuMGF were equally effective in the enhancement of human bone marrow colony formation, but rhuMGF, in contrast to rmuMGF, did not at the concentrations tested enhance colony formation by mouse bone marrow cells. MGF effects on BFU-E, CFU-GM, and CFU-GEMM may be direct acting ones as MGF-enhanced colony formation by these cells in highly enriched progenitor cell populations of CD34 HLA-DR+ and CD34 HLA-DR+CD33- sorted cells in which greater than or equal to 1 of 2 cells was a BFU-E plus CFU-GM plus CFU-GEMM. MGF appears to be an early acting cytokine that preferentially stimulates the growth of immature hematopoietic progenitor cells.
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PMID:Effect of murine mast cell growth factor (c-kit proto-oncogene ligand) on colony formation by human marrow hematopoietic progenitor cells. 170 71

Our experiments were directed towards the detection of the influence of interleukin-1 (IL-1); interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the generation of granulocyte-macrophage progenitor cells. We also set out to examine whether this process is connected with changes within the early precursor cell compartment. Bone marrow suspension cultures (12 days) supplemented with these cytokines were tested for the presence of GM colony-forming cells (GM-CFC) in a colony-forming unit assay. The percentage of CD34+ and HLA-DR+ as well as the number of blasts and promyelocytes were estimated cytofluorometrically and morphologically. The proliferative effect of GM-CSF was associated with a net increase of GM-CFC and HLA-DR+ myeloid cells and a decrease in the percentage of CD34+ early precursor cells. IL-3 acted similarly and also caused an absolute decrease of CD34+ cells in the cultures. IL-1 did not stimulate the generation of blasts or GM-CFC but elevated the number of CD34- as well as HLA-DR-expressing cells in the cultures. These results imply that GM-CSF supported the maintenance of hematopoiesis in vitro. The transition from early precursor cells to committed myeloid progenitor cells (GM-CFC) and more mature precursor cells (G-CFC, M-CFC) may be supported by GM-CSF without affecting the self-renewing capacity of CD34+ early precursors. In contrast, the blast-generating and proliferation-inducing action of IL-3 is associated with a drop in the total number of CD34+ stem cells. An efficient renewal of this population obviously depends on the presence of IL-1.
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PMID:Comparative analysis of the influences of IL-1, IL-3 and GM-CSF on the commitment of granulocyte-macrophage progenitors in vitro. 172 Mar 32

An in vitro colony assay was used to examine the growth stimulatory effects of a variety of recombinant human lymphohemopoietic cytokines on human precursor-B acute lymphoblastic leukemia (ALL) cells. Of 23 cases evaluated, 16 formed significant numbers of colonies (mean 280, range 36-939) when cultured in 10% fetal calf serum in 0.8% methylcellulose containing 10% partially purified B-cell growth factor (BCGF). Immunoperoxidase staining of cells from cultures confirmed a precursor-B phenotype (HLA-DR+, CD-10+, CD-19+, CD-34+, Ig-, CD-3-, CD-11C-). When these cases were cultured with recombinant human cytokines (but without BCGF) only a minority showed colony formation, in all instances less than seen with BCGF. Three cases were stimulated both by interleukin 3 (IL-3) and the putative pre-B growth factor interleukin 7 (IL-7). One case was stimulated both by tumor necrosis factor alpha and by interleukin 6 (IL-6); these results were confirmed on highly purified CD-10+, CD-19+ cells prepared by fluorescence-activated cell sorting. A further case was stimulated by granulocyte-macrophage colony-stimulating factor (GM-CSF), including CD-10+, CD-19+ purified cells. All cases responding to recombinant cytokines were heavily pretreated patients at relapse, whereas none of the newly diagnosed untreated cases showed any response. These results confirm that activities present in BCGF are the major stimulant for precursor-B ALL proliferation in vitro. None of the recombinant cytokines examined, including IL-7, appeared to have consistent activity under these culture conditions. The molecules regulating growth of ALL remain to be more precisely defined.
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PMID:Effects of recombinant human cytokines on precursor-B acute lymphoblastic leukemia cells. 189 54

Forty-seven patients with hematologic neoplasia received recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) by daily 2-hour infusion following allogeneic bone marrow transplantation from HLA-identical sibling donors in a phase I-II dose-escalation trial. Dose levels ranged from 30 to 500 micrograms/m2/d. At doses at or below 250 micrograms/m2/d, toxicity felt to be caused by rhGM-CSF was negligible. However, three of five patients treated with 500 micrograms/m2/d had unacceptable side effects caused by rhGM-CSF. Two different graft-versus-host disease (GVHD) prophylactic regimens were administered. Twenty-seven evaluable patients were administered regimens that did not contain methotrexate (MTX) (Group I) and reached an absolute neutrophil count of 1,000/microL by a median of day 14. In contrast, 18 patients who received GVHD prophylactic regimens containing MTX (Group II) reached an absolute neutrophil count of 1,000/microL on a median of day 20. Patients in Group I had fewer febrile days and, of those discharged, had shorter initial hospitalizations than patients in Group II. The overall incidence of severe acute GVHD (grade 2 or greater) in the rhGM-CSF-treated patients was 28% and was similar to that in historical "good risk" patients who did not receive rhGM-CSF. These preliminary data suggest rhGM-CSF is unlikely to exacerbate GVHD in HLA-identical sibling donor transplants and indicate the need for randomized trials of rhGM-CSF in allogeneic marrow transplant patients.
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PMID:Phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor following allogeneic bone marrow transplantation. 190 25


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