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PubMed1981

Colony forming units in culture and colony stimulating activity of systemic lupus erythematosus.

The bone marrow granulocyte-macrophage progenitor cells (CFU-C) in patients with systemic lupus erythematosus (SLE) were estimated according to the double-layer soft agar system of Pike and Robinson. When nucleated narrow cells from patients with SLE were cultured with peripheral leukocytes from normal donors as a source on colony stimulating activity (CSA), colony counts (the term colony indicating aggregates of more than 50 cells) in active SLE were reduced significantly but cluster counts (cluster: 10 to 50 cells) were divided into two groups of markedly increased and decreased clusters. When normal nucleated marrow cells were cocultured in the overlayer with peripheral leukocytes of patients with SLE in he feeder layer, colony counts decrease significantly but cluster counts remained within the normal range. When CFU-C by normal nucleated marrow cells were studied in the presence of PHA- or LPS-induced CSA of peripheral leukocytes from patients with SLE, total colony and cluster counts decreased. These data indicate the granulomonocytopenia in SLE may result from the diminution of production of CSA in peripheral leukocytes and/or the direct impairment of growth and differentiation in progenitor cells of granulocytes and macrophages.

Adult↗
PubMed1993

Granulocytic-macrophagic and macrophagic colony stimulating factors elicit colonies of mast cells in mouse bone marrow agar culture. An electron microscope study.

Granulocytic-macrophagic colony stimulating factor (GM-CSF) and macrophagic colony stimulating factor (M-CSF or CSF-1) stimulate bone marrow cells of mouse to produce in semisolid agar colonies in which mononuclear cells were reported to be macrophages. We verified in such colonies the ultrastructure of the mononuclear cells which had cytoplasmic granules of the mast cells and lacked lysosomes, therefore we considered them as mast cells. However, the granules content did not reach the degree of condensation typically found in granules of mouse peritoneal mature mast cells. The mast cells of colonies obtained in agar can be mast cells arrested at some point in the maturative process, mast cells of a yet unrecognized type or cells with mast cells ultrastructural features which behave as precursors for cells of myeloid lineage.

Agar↗
PubMed1997

Interleukin-10 inhibits spontaneous colony-forming unit-granulocyte-macrophage growth from human peripheral blood mononuclear cells by suppression of endogenous granulocyte-macrophage colony-stimulating factor release.

Spontaneous growth of myeloid colonies (colony-forming unit-granulocyte-macrophage [CFU-GM]) can be observed in methylcellulose cultures containing peripheral blood mononuclear cells (PB-MNCs) and is supposedly caused by the release of colony-stimulating factors (CSF) by accessory cells. Because of its cytokine synthesis-inhibiting effects on T lymphocytes and monocytes, interleukin-10 (IL-10) may be a potential candidate for indirect modulation of hematopoiesis. We studied the effect of recombinant human IL-10 (rhIL-10) on spontaneous growth of myeloid colonies derived from human PB-MNCs. A total of 10 ng/mL of IL-10 almost completely inhibited spontaneous CFU-GM proliferation (by 95.1%; P < .001, n = 7) in unseparated PB-MNCs. This effect was dose-dependent and specific, because a neutralizing anti-IL-10 antibody was able to prevent IL-10-induced suppression of CFU-GM growth. Spontaneous CFU-GM growth, which required the presence of both monocytes (CD14+ cells) and T lymphocytes (CD3+ cells), was also greatly suppressed by a neutralizing anti-granulocyte-macrophage CSF (GM-CSF) antibody but was only slightly or not at all inhibited by antibodies against G-CSF or IL-3. Moreover, IL-10-suppressed colony growth could be completely restored by the addition of exogenous GM-CSF. Using semiquantitative polymerase chain reaction, we were able to show that GM-CSF transcripts that spontaneously increased in PB-MNCs within 48 hours of culture were markedly reduced by the addition of IL-10. Inhibiton of GM-CSF production in PB-MNCs by IL-10 was also confirmed at the protein level by measuring GM-CSF levels in suspension cultures. Our findings suggest that autonomous CFU-GM growth, resulting from an interaction of monocytes and T lymphocytes, is mainly caused by endogenous GM-CSF release and can be profoundly suppressed by the addition of exogenous IL-10. Considering the strong inhibitory action of IL-10 on GM-CSF production and spontaneous cell growth in vitro, this cytokine may be useful in myeloid malignancies in which autocrine and/or paracrine mechanisms involving GM-CSF are likely to play a pathogenetic role.

Cell Differentiation↗
PubMed1997

Flt3 ligand synergizes with granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor to mobilize hematopoietic progenitor cells into the peripheral blood of mice.

Peripheral blood progenitor cells (PBPC) are increasingly being used in the clinic as a replacement for bone marrow (BM) in the transplantation setting. We investigated the capacity of several different growth factors, including human flt3 ligand (FL), alone and in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF ) or granulocyte colony-stimulating factor (G-CSF ), to mobilize colony forming cells (CFU) into the peripheral blood (PB) of mice. Mice were injected subcutaneously (SC) with growth factors daily for up to 10 days. Comparing the single agents, we found that FL alone was superior to GM-CSF or G-CSF in mobilizing CFU into the PB. FL synergized with both GM-CSF or G-CSF to mobilize more CFU, and in a shorter period of time, than did any single agent. Administration of FL plus G-CSF for 6 days resulted in a 1,423-fold and 2,717-fold increase of colony-forming unit-granulocyte-macrophage (CFU-GM) and colony-forming unit granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM) in PB, respectively, when compared with control mice. We also followed the kinetics of CFU numerical changes in the BM of mice treated with growth factors. While GM-CSF and G-CSF alone had little effect on BM CFU over time, FL alone increased CFU-GM and CFU-GEMM threefold and fivefold, respectively. Addition of GM-CSF or G-CSF to FL did not increase CFU in BM over levels seen with FL alone. However, after the initial increase in BM CFU after FL plus G-CSF treatment for 3 days, BM CFU returned to control levels after 5 days treatment, and CFU-GM were significantly reduced (65%) after 7 days treatment, when compared with control mice. Finally, we found that transplantation of FL or FL plus G-CSF-mobilized PB cells protected lethally irradiated mice and resulted in long-term multilineage hematopoietic reconstitution.

Animals↗
PubMed1994

Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on neutrophil formation and function.

Work published in the past year has significantly increased our understanding of the intracellular signaling pathways that are activated following granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor binding to cell surface receptors. The involvement of nonreceptor protein tyrosine kinases, in particular the JAK2 kinase, appears to be a major signal transduction pathway involved in the response to several hemopoietic cytokines. Further data continue to accrue on the clinical role of granulocyte colony-stimulating factor, in particular in the treatment of chronic neutropenia. Increased clinical experience with colony-stimulating factors has revealed side effects that may occur with chronic use. The effects of colony-stimulating factors on neutrophil function are shown increasingly to be complex and to involve significant interactions with other proinflammatory cytokines.

Agranulocytosis↗
PubMed1994

Granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor, PIXY-321, stem cell factor, interleukin-3, and interleukin-7: receptor binding and effects on clonogenic proliferation in acute lymphoblastic leukemia.

Cytokines are frequently used after chemotherapy of leukemias and solid tumors to augment recovery of normal hematopoiesis. While the regulation of normal and leukemic myelopoiesis is well investigated, little is known about effects of cytokines on growth and differentiation of lymphoblastic leukemia. In this study, we investigated the expression of receptors for G-CSF, GM-CSF, SCF, IL-3, and IL-7 on acute lymphoblastic leukemia (ALL) blasts and the effects of these growth factors (GF) on ALL blast colony formation. The binding of fluorescence-tagged cytokines to receptors on ALL blasts was studied by flow-cytometry in 27 cases of ALL (24 precursor B-ALL, 3 T-ALL). Receptor-binding for myeloid-associated GF was observed in the majority of precursor B-ALL (G-CSF = 100%, GM-CSF = 65%, IL-3 = 83%, SCF = 74%), but not in T-ALL. Binding of labelled IL-7 was detected in both precursor B- (92%) and T-ALL (100%). The presence of receptors for SCF in ALL was confirmed by polymerase chain reaction for c-kit mRNA in 19/21 cases tested. Expression of receptors for G-CSF, GM-CSF, IL-3, and SCF was not associated with expression of myeloid antigens, or with specific cytogenetic abnormalities. The effects of these GF on clonogenic cells were tested in the ALL blast colony assay and varied between samples, but all cytokines were able to increase clonogenic growth. The GM-CSF/IL-3 fusion molecule PIXY-321 was most effective in promoting colony growth. In some cases inhibition of colony formation was found. We conclude that ALL blast cells have receptors not only for IL-7, but also for G-CSF, GM-CSF, SCF, and IL-3. ALL precursors can respond to these GF with changes in their clonogenic growth indicating the presence of functional receptors. Results may have implications for therapeutic approaches combining cytokines and chemotherapy.

Adolescent↗
PubMed1989

Granulocyte-macrophage colony-stimulating factor requires interaction with accessory cells or granulocyte-colony stimulating factor for full stimulation of human myeloid progenitors.

Human recombinant GM-CSF (rGM-CSF) was tested on highly purified and fractionated CFU-GM subsets. The fractionation was performed with the DS1-1 monoclonal antibody (MoAb), which distinguishes early and late CFU-GM. On whole bone marrow cells, rGM-CSF had a colony-stimulating activity comparable to that of known sources of CSFs, ie, the supernatant (SN) of TPA 30-1 or 5637 cell lines, used as control. A greatly reduced activity was observed when CFU-GM were depleted of phagocytizing and E rosetting cells (colony growth of 27% as compared with control). On fractionated CFU-GM, the rGM-CSF activity was even more reduced on both early and late progenitors (18% and 6% of colony growth, respectively). However, when rGM-CSF was used together with rG-CSF at suboptimal concentrations, the colony growth reached values analogous to that of control cultures. A synergistic interaction between rGM-CSF and rG-CSF in stimulating either early or late myeloid progenitors was observed. The results suggest that the activity of rGM-CSF on CFU-GM is mainly exerted through cooperation with accessory cells. r-G-CSF is one of the factors that can synergistically cooperate with r-GM-CSF in the myelopoietic stimulation.

Bone Marrow↗
PubMed2006

Colony stimulating factors (including erythropoietin, granulocyte colony stimulating factor and analogues) for stroke.

BACKGROUND: Colony stimulating factors (CSFs), also called haematopoietic growth factors, regulate bone marrow production of circulating red and white cells, and platelets. They have been shown to be neuroprotective in experimental stroke. Some CSFs also mobilise the release of bone marrow stem cells into the circulation. OBJECTIVES: We systematically assessed the effects of CSFs on functional outcome and haematology measures in patients with acute or subacute stroke enrolled into randomised controlled trials. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched February 2005), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005), MEDLINE (1985 to March 2006), EMBASE (1985 to November 2005), and Science Citation Index (1985 to November 2005). In an attempt to identify further published, unpublished and ongoing trials we contacted manufacturers and principal investigators of trials (last contacted 2005). We also searched reference lists of relevant articles and reviews. SELECTION CRITERIA: Unconfounded randomised controlled trials recruiting patients with acute or subacute ischaemic or haemorrhagic stroke were included. CSFs included stem cell factor (SCF), erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF, CSF-1), and thrombopoietin (TPO), or analogues of these. The primary outcome was functional outcome (assessed as combined death or disability and dependency using scales such as the modified Rankin Scale or Barthel Index) at the end of the trial. Secondary outcomes included safety at the end of treatment (death, impairment, deterioration, extension or recurrence), death at the end of follow up, and haematology measures (blood counts at or around day seven after treatment commenced). DATA COLLECTION AND ANALYSIS: Data on measures by intention to treat (where available) were collected and analysed as dichotomous or continuous outcomes, as relevant, using random-effects models. Heterogeneity was assessed. MAIN RESULTS: No large trials were identified. EPO therapy was associated with a non-significant reduction in neurological impairment in one small trial (n = 40 participants) but had no significant effect on haematological measures. Further small trials of EPO and G-CSF are ongoing. AUTHORS' CONCLUSIONS: No large trials of EPO, G-CSF or other colony stimulating factors have been performed and it is too early to know whether CSFs improve functional outcome.

Colony-Stimulating Factors↗
PubMed1983

Inhibition of murine CFU-C by vindesine: restoration of colony growth by colony stimulating factor.

Vindesine (VDS) is a new vinca-alkaloid related to vinblastine and vincristine that blocks production of the microtubules in the mitotic phase of the cell cycle. Studies were undertaken to investigate the inhibitory effect of VDS on normal murine bone marrow cell proliferation and the possible interactions between this compound and L-cell derived colony stimulating factor (CSF). One X 10(7) murine bone marrow cells were exposed to various concentrations of VDS, ranging from 0.1 to 1.5 micrograms/ml for 1 h at 37 degrees C. Following this period, the cells were plated in agar in the presence of 100 units of CSF. A dose-dependent inhibition of colony formation was noted with increasing doses of the drugs. To determine whether an increased dose of CSF could overcome the inhibitory effect of VDS, further studies compared colony growth in response to 100 and 200 units of CSF. Virtually no inhibition of colony growth was detected in VDS-treated cells exposed to this higher dose of CSF while a dose-dependent reduction in CFU-C was noted with 100 units of CSF. Preincubation of cells with VDS and CSF prevented the inhibition that occurred with VDS alone. The addition of anti-CSF serum during the preincubation phase abolished the protective effect of CSF. The studies show that short-term exposure of marrow cells to VDS causes a dose-dependent inhibition of in vitro colony formation; this inhibition is prevented by increasing doses of CSF in agar culture or by simultaneous preincubation with CSF. The CSF action appears specific as its protective effect is neutralized by antibody to CSF, suggesting a potential role for CSF in preventing the antimitotic activity of VDS.

Animals↗
PubMed2006

Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial.

OBJECTIVES: The purpose of this investigator-driven, prospective, randomized, double-blinded, placebo-controlled phase II study was to compare the effects of granulocyte colony-stimulating factor (G-CSF) on the improvement of myocardial function in patients undergoing delayed percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Experimental and early clinical studies suggest that transplantation of stem cells improves cardiac regeneration and neovascularization after acute myocardial infarction. Most investigators have utilized either a direct injection or intracoronary infusion of bone marrow-derived cells, but early cytokine-mediated mobilization of stem cells has been reported to show similar improvement in cardiac function. METHODS: Forty-four patients with late revascularized subacute STEMI were treated either with G-CSF or placebo over 5 days after successful PCI. Primary end points were change of global and regional myocardial function from baseline (1 week after PCI) to 3 months after PCI assessed by magnetic resonance imaging (MRI). Secondary end points consisted of characterization of mobilized stem cell populations, assessment of safety parameters up to 12 months including 6-month angiography, as well as myocardial perfusion assessed by MRI. RESULTS: Global myocardial function from baseline (1 week after PCI) to 3 months improved in both groups, but G-CSF was not superior to placebo (Delta(ejection fraction) 6.2 +/- 9.0 vs. 5.3 +/- 9.8%, p = 0.77). A slight but non-significant improvement of regional function occurred in both groups. Granulocyte colony-stimulating factor resulted in mobilization of endothelial progenitor cell populations and was well tolerated with a similar rate of target lesion revascularization from in-stent restenosis. In both groups major adverse cardiovascular events occurred in a comparable frequency. Granulocyte colony-stimulating factor resulted in significant improvement of myocardial perfusion 1 week and 1 month after PCI. CONCLUSIONS: Granulocyte colony-stimulating factor treatment after PCI in subacute STEMI is feasible and relatively safe. However, patients do not benefit from G-CSF when PCI is performed late. Granulocyte colony-stimulating factor results in improved myocardial perfusion of the infarcted area, which may reflect enhanced neovascularization.

Angioplasty, Balloon, Coronary↗
PubMed1986

Soft agarose colony formation assay for human renal cell carcinoma: comparison of optical colony counting versus tritiated thymidine incorporation.

Use of the Hamburger-Salmon soft agar assay method for in vitro chemotherapy sensitivity testing of samples of renal cell carcinoma has been somewhat limited by a relatively low proliferation/evaluability rate for this tumor type (approximately 50%). The tritiated thymidine ([ 3H]-TdR) incorporation assay method of Tanigawa et al. (Cancer Res., 42: 2159, 1982) was compared to a standard optical colony counting assay technique. Fifty-seven different primary and five metastatic fresh samples of human renal cell carcinoma were studied. Evaluability rate by the [3H]-TdR assay was 90% (greater than or equal to 300 cpm control). In comparison, evaluability rate by optical colony counting was 43% for this group of tumors. [3H]-TdR incorporation increased with increasing tumor grade and increasing stage. Spindle cell tumors showed significantly higher cpm than other cell types. Twenty-three primary tumors were evaluable by both [3H]-TdR and colony counting methods. The correlation coefficient ("r") for regression lines for drug sensitivity data points (optical counting vs. [3H]-TdR) of these individual experiments ranged from 0.50 to 0.99 with a mean r +/- S.D. of 0.76 +/- 0.15. For all 260 paired drug response observations of 23 tumors exposed to different drugs, the correlation was very good with r = 0.71. Since the [3H]-TdR assay has an evaluability rate of approximately 90% for renal cell carcinoma, gives drug sensitivity information which correlates well with the colony counting endpoint and yields chemotherapy sensitivity information four days after sample accession, the [3H]-TdR assay may be a more useful method for study of human renal cell carcinoma in vitro chemotherapy sensitivity testing than standard colony counting techniques.

Antineoplastic Agents↗
PubMed1994

Expression of an activated erythropoietin or a colony-stimulating factor 1 receptor by pluripotent progenitors enhances colony formation but does not induce differentiation.

Whether the presence of specific receptors on the surface of developing cells is the cause or consequence of lineage restriction is not known. If activation of specific receptors is the driving event in differentiation, the premature expression of specific receptors would promote differentiation along that pathway. In this study pluripotent progenitors, obtained from blast cell colonies (pooled or individual) of 5-fluorouracil-treated mice, were infected with retroviral vectors containing either an activated receptor for erythropoietin (EPO), an erythroid progenitor growth factor, or the receptor for colony-stimulating factor 1 (CSF-1), a macrophage growth factor. These receptors exhibit expression patterns restricted to committed progenitors. The developmental potential of infected pluripotent progenitors was not changed, although they expressed the exogenous genes, suggesting that in these cells activation of lineage-specific receptors does not induce differentiation. Acquisition of a constitutively activated EPO receptor allowed erythroid development in mixed colonies in the absence of EPO, as expected. Infection of progenitors with a virus containing the CSF-1 receptor promoted the development of granulocyte/macrophage (GM) colonies but did not alter the differentiation potential of either colony-forming unit (CFU)-GM or CFU-mix.

Animals↗
PubMed1985

Inhibition of bone marrow colony formation by human natural killer cells and by natural killer cell-derived colony-inhibiting activity.

Incubation of human peripheral blood lymphocytes with bone marrow cells resulted in significant inhibition of colony formation by committed myeloid and erythroid cells. Using positively selected homogeneous natural killer (NK) cell preparations and lymphocyte subpopulations depleted of or enriched for NK cells, we definitively characterize as NK cells the cells in normal peripheral blood that are responsible for inhibition of bone marrow colony growth. The inhibitory effect of NK cells on hematopoiesis can be mediated by a soluble factor that is produced only by NK cells upon culture with HLA-DR+ hematopoietic cells and with NK-sensitive cell lines. Both NK cells and the NK-produced, colony-inhibiting activity (NK-CIA) are suppressive for allogeneic and autologous bone marrow CFU-GEMM (colony-forming units, granulocyte, erythroid, monocyte, megakaryocyte), CFU-E (CFU, erythroid), and early CFU-GM (CFU, granulocyte, monocyte), but not for either BFU-E (burst-forming units, erythroid) or late CFU-GM. [3H]Thymidine incorporation was inhibited by NK-CIA-containing supernatants in HLA-DR+ but not HLA-DR- bone marrow cell populations stimulated to proliferative by colony-stimulating factor (CSF). These data suggest that the NK cell-mediated inhibitory effect on proliferation and differentiation of hematopoietic precursor cells is mediated in part or completely by the secreted NK-CIA. The concentration of NK-CIA reached in the supernatant of the mixture of NK cell-containing lymphocyte populations with bone marrow cells is sufficient to account for the inhibitory effect mediated by NK cells. Our data support the hypothesis that human NK cells play a major role in the control of hematopoiesis, down-regulating it under conditions in which the NK cells are functionally activated.

Animals↗
PubMed1977

Bone marrow colony-forming cells in mice with virus-induced lymphoid leukemia: relation to serum colony-stimulating activity and blood granulocytes.

Mice with advanced lymphoid leukemia have elevated peripheral blood granulocytes and elevated serum colony-stimulating activity, which promotes the in vitro growth of granulocyte and/or macrophage colonies. The number of bone marrow precursor cells of the in vitro granulocyte and/or macrophage colonies varied from normal to 10% of normal. The elevation of colony-stimulating activity correlated best with a combination of increased blood granulocytes and a deficiency of bone marrow precursor cells, which suggested that colony-stimulating activity is a leukopoietin that increases the efficiency and rate of production of granulocytes.

Animals↗
PubMed2000

Large macrophage colony-forming cells identical to high proliferative potential colony-forming cells in peripheral blood of patients with collagen vascular diseases: high occurrence among patients with systemic sclerosis and dermatomyositis.

OBJECTIVE: To examine peripheral blood (PB) of patients with various collagen vascular diseases (CVD) for the presence of colony-forming cells (CFC) that form large macrophage colonies (> 2.5 mm in diameter, > 10,000 cells). METHODS: Peripheral blood mononuclear cells were obtained from 92 patients with various active CVD and 20 healthy controls, and assayed for in vitro colony formation. There were 14 patients with systemic lupus erythematosus (SLE), 30 with rheumatoid arthritis (RA), 17 with systemic sclerosis (SSc), 20 with polymyositis (PM)/dermatomyositis (DM) (11 PM, 9 DM) and 11 with systemic vasculitis. RESULTS: Large macrophage CFC were detected in PB of 7% of patients with SLE (1/14), 17% with RA (5/30), 47% with SSc (8/17), 30% with PM/DM (6/20) [9% PM (1/11) and 56% DM (5/9)], 0% of those with systemic vasculitis (0/11) and 0% of the healthy subjects (0/20). There was a significant difference between the occurrence of CFC in patients with PM versus patients with DM (p < 0.05). The occurrence of CFC in patients with SSc or DM was significantly higher than that in patients with other CVD including SLE, RA, PM, and systemic vasculitis (p < 0.05). CONCLUSION: Based on the size of the colonies they formed, the CFC corresponded to high proliferative potential colony-forming cells, a subset of primitive hematopoietic cells. Our findings among patients with CVD indicate that these primitive hematopoietic progenitor cells, which are believed to constitute a noncirculating population in healthy individuals, are found most frequently in PB of patients with SSc and DM. It is likely that primitive hematopoietic cells are frequently mobilized into the peripheral circulation during the pathogenesis of SSc and DM.

Arthritis, Rheumatoid↗
PubMed1990

Stimulation of human T cell colony growth by a lymphocyte colony enhancement factor derived from lymphocyte subpopulations.

Blood mononuclear cells (MNC) develop into T cell colonies when the cells are sensitized with PHA and seeded in a two-layer soft agar system. Conditioned medium (CM) derived from MNC enhanced lymphocyte colony formation when it was added to the culture system. CFU-TL appear to be stimulated into colony formation by molecules secreted by lymphocyte subpopulations contained in the seeded cells. In this study, human peripheral blood MNC were fractionated by a battery of techniques into adherent, E+, CD4+, CD8+, B and null cells. CM was prepared from each of the subpopulations and its effects on T cell colony growth assayed. All the lymphocyte subpopulations were found to generate lymphocyte colony enhancement factor (LCEF). After several purification procedures, CM prepared from CD4 and CD8+, displayed LCEF activity corresponding to proteins of molecular weight 30-40 and 100-140 kD.

Antigens, CD↗
PubMed1989

Recombinant and native human urinary colony-stimulating factor directly augments granulocytic and granulocyte-macrophage colony-stimulating factor production of human peripheral blood monocytes.

Colony-stimulating factor from human urine (CSF-HU) has been purified to a homogeneous protein, and its complementary DNA (cDNA) has been cloned. Recombinant CSF-HU was prepared from a serum-free medium conditioned by Chinese hamster ovary cells transfected with the cDNA and purified by the same method as that for the native protein. Purified CSF-HU stimulated human bone marrow cells to form macrophage colonies. It also stimulated human mature monocytes prepared from peripheral blood of healthy volunteers to produce human active colony-stimulating activity that stimulates human bone marrow cells to form granulocyte and macrophage colonies. This activity was partially neutralized by the addition of both polyclonal antibodies against human granulocyte colony-stimulating factor and against human granulocyte-macrophage CSF, respectively. The stimulation of monocytes by CSF-HU was not inhibited by the addition of polymyxin-B, which is known as a potent inhibitor of endotoxin. On the other hand, CSF-HU did not stimulate monocyte production of interleukin-1 and interferon. These results indicate that recombinant and native CSF-HU stimulates immature cells as well as mature cells in the human monocyte lineage.

Cell Differentiation↗
PubMed1987

Effects of granulocyte-macrophage colony-stimulating factor and erythropoietin on leukemic erythroid colony formation in human early erythroblastic leukemias.

Erythroid colonies from five patients with an early erythroblastic leukemia were obtained in "serum-free" cultures in the presence or absence of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) and homogeneous native erythropoietin (Epo). Erythroid colonies with abnormal morphology and karyotype could be grown in different culture conditions. Their erythroid nature was ascertained by the presence of carbonic anhydrase I and glycophorin A. Leukemic erythroid progenitors strongly differed from normal progenitors in that spontaneous colonies were always obtained, sometimes with an extremely high plating efficiency (up to 5.7%). Colonies were found to be autonomous from exogenous hematopoietic growth factors because they were still obtained with a high plating efficiency at an average of one cell per culture in the absence of any added growth factor. No evidence for an autocrine secretion of Epo or GM-CSF emerged because Epo or GM-CSF could not be detected by biologic or radioimmunologic assays from the culture supernatant or cellular extracts of the leukemic cells and that Epo or GM-CSF antibodies did not block autonomous growth. In all cases, however, hematopoietic growth factors increased the plating efficiency of the abnormal erythroid progenitors. In the two "de novo" leukemias, leukemic erythroid progenitors responded primarily to Epo, whereas in the three other patients' (chronic myeloid leukemia) blast crisis they responded maximally to GM-CSF plus Epo. Recombinant erythroid-potentiating activity had no effect in any of these cases. These results suggest that the leukemic erythroid clonogenic cells arise from expansion of erythroid progenitors at different levels of differentiation (ie, CFU-E or BFU-E, depending upon the disease) and that autonomous growth is not related to a secretion of Epo or GM-CSF.

Cell Cycle↗