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Biomedical subjects

H E Broxmeyer

Publications and source records attributed to H E Broxmeyer.

At least 199 records · Page 11Linked to original sources
PubMed1993

Human interferon-inducible protein 10: expression and purification of recombinant protein demonstrate inhibition of early human hematopoietic progenitors.

Human interferon-inducible protein 10 (IP-10), a member of the family of the small secreted proteins called intercrine cytokines or chemokines, is secreted by interferon gamma-stimulated T cells, monocytes, endothelial cells, and keratinocytes. We have begun to explore the biological properties of IP-10 by cloning and overexpression in baculovirus and in bacterial protein expression systems. A 9.9-kD protein was secreted by infected insect cells, which on sodium dodecyl sulfate-polyacrilamide gel electrophoresis comigrated with keratinocyte IP-10 and with f(22-98), a bacterial recombinant fragment lacking the signal sequence but containing all other residues of IP-10. All three reacted with antibodies recognizing residues 10-98 (alpha IP-10) and 77-98 of IP-10 (alpha 22), demonstrating that it is secreted by keratinocytes and insect cells after removal of the signal sequence but without proteolysis of the COOH-terminal end. Purified rIP-10 suppresses in vitro colony formation by early human bone marrow progenitor cells which need r-steel factor (rSLF) and rGM-CSF or rSLF and r-erythropoeitin (rEPO). The inhibition is dose dependent, is complete at concentrations > or = 50 ng/ml, is prevented by preincubation of rIP-10 with alpha IP-10, but not by alpha 22, and is seen with highly purified CD34+ cells, suggesting direct effect of rIP-10 on the progenitors. Combination of rIP-10 and other chemokines at inactive concentrations inhibited colony formation in a synergistic manner. rIP-10 did not affect colony formation in the absence of any growth factors or in the presence of rEPO or rGM-CSF but in absence of rSLF. The effects of IP-10 may be relevant to normal marrow function and might be harnessed to protect human hematopoietic progenitors from the cytotoxic effects of chemotherapy.

Amino Acid Sequence↗
PubMed1993

Comparative analysis of the human macrophage inflammatory protein family of cytokines (chemokines) on proliferation of human myeloid progenitor cells. Interacting effects involving suppression, synergistic suppression, and blocking of suppression.

Macrophage inflammatory protein (MIP)-1 alpha, part of a family termed chemokines, has been implicated in suppression of hemopoietic stem and progenitor cell proliferation. The chemokine family has been organized into two subgroups with MIP-1 alpha, MIP-1 beta, macrophage chemotactic and activating factor (MCAF) and RANTES belonging to one subgroup, and GRO-alpha, MIP-2 alpha (GRO-beta), MIP-2 beta (GRO-gamma), platelet factor 4 (PF4), IL-8, and neutrophil activating peptide (NAP)-2 belonging to the other. These molecules were evaluated for effects on colony formation by human bone marrow multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. None of the chemokines stimulated colony formation in the absence of CSF, or influenced colony formation stimulated by a single growth factor such as granulocyte-macrophage-CSF or erythropoietin. However, MIP-1 alpha, MIP-2 alpha, PF4, IL-8, and MCAF suppressed in dose-response fashion colony formation of immature subsets of myeloid progenitor cells stimulated by GM-CSF plus steel factor. Effects were apparent on low density and CD34 HLA-DR(+)-sorted marrow cells in which up to 88.4% of the cells were composed of progenitor cells, suggesting direct effects on the progenitors themselves. Up to 2500-fold less of each chemokine could be used to demonstrate synergistic suppression when any two of these five chemokines were used together at low concentrations, effects also apparently directly on the progenitors. In contrast, MIP-1 beta, MIP-2 beta, GRO-alpha, NAP-2, and RANTES were not suppressive nor did they synergize with MIP-1 alpha, MIP-2 alpha, PF4, IL-8, or MCAF to suppress. However, a fivefold excess of MIP-1 beta blocked the suppressive effects of MIP-1 alpha. Similarly, a fivefold excess of either MIP-2 beta or GRO-alpha blocked the suppressive effects of IL-8 and PF4. These suppressing, synergizing and blocking effects may be of relevance to blood cell regulation.

Animals↗
PubMed1993

Polymerization of murine macrophage inflammatory protein 1 alpha inactivates its myelosuppressive effects in vitro: the active form is a monomer.

Macrophage inflammatory protein (MIP) 1 alpha has myelosuppressive and myeloprotective activity. That MIP-1 alpha polymerizes is known; this phenomenon was evaluated in terms of myelosuppression by assessing the effects of recombinant murine MIP-1 alpha on colony formation of murine and human myeloid progenitor cells in vitro. The following results are reported: (i) Polymerization is diluent- and concentration-dependent. (ii) Monomeric MIP-1 alpha is the active suppressive form for myeloid progenitor cells in vitro. (iii) Polymerized MIP-1 alpha is inactive and does not interfere with suppression by monomeric MIP-1 alpha. (iv) MIP-1 alpha has approximately 1000-fold higher specific activity than has been reported, but its effects are still specific for immature subsets of myeloid progenitors. (v) Suppression is initiated during the DNA-synthesis phase of the cell cycle. We conclude that polymerization of MIP-1 alpha might be a control mechanism that limits the myelosuppressive effects of monomeric MIP-1 alpha.

Animals↗
PubMed1993

Human multipotential progenitor cells (CFU-GEMM) have extensive replating capacity for secondary CFU-GEMM: an effect enhanced by cord blood plasma.

The replating capability of human umbilical cord blood (CB) multipotential (CFU-GEMM) progenitors was assessed in vitro as an estimate of self-renewal using erythropoietin (Epo), steel factor (SLF), and either fetal bovine serum (FBS) or CB plasma. This study found a much higher replating efficiency for CB CFU-GEMM than previously reported, in terms of the percentage of colonies that could be replated, the number of secondary colonies per replated primary colony, and the size of secondary colonies. Moreover, the majority of secondary colonies were CFU-GEMM-derived. Although the percentages of bone marrow CFU-GEMM that replate was similar to that for CB CFU-GEMM and the sizes of secondary bone marrow and CB CFU-GEMM were also similar, replated CB CFU-GEMM gave rise to far greater numbers of secondary colonies. No tertiary colonies were observed when secondary CFU-GEMM were replated. Detection of extensive secondary replating potential was enhanced by the addition of CB plasma to the cultures. This activity was not found in either adult blood (PB) plasma, umbilical cord vein endothelial cell-conditioned medium (ECCM), FBS plus ECCM, or FBS plus the combination of interleukin-1 (IL-1), IL-3, IL-6, IL-11, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Whether the CB plasma-enhancing activity for CFU-GEMM replating capacity is attributable to a novel factor or factors, or represents effects of other known cytokines, alone or in combination, remains to be determined. Of particular relevance, these studies suggest that human CFU-GEMM have some degree of stemness and perhaps should be classified as a subset of stem cells.

Bone Marrow Cells↗
PubMed1993

In vivo effects of recombinant interleukin-11 on myelopoiesis in mice.

Purified recombinant human interleukin-11 (rhuIL-11) was assessed for its in vivo effects on the proliferation and differentiation of hematopoietic progenitors as well as its capacity to accelerate the recovery of a drug-suppressed hematopoietic system. Dosage and time sequence studies demonstrated that administration of IL-11 to normal mice resulted in increases in absolute numbers of femoral marrow and splenic myeloid (granulocyte-macrophage colony-forming unit [CFU-GM], burst-forming unit-erythroid [BFU-E], CFU-granulocyte, erythroid, macrophage, megakaryocyte) progenitor cells and in stimulation of these progenitors to a higher cell cycling rate. This was associated with increased numbers of circulating neutrophils. Administration of IL-11 to mice pretreated with cyclophosphamide decreased the time required to regain normal levels of neutrophil and platelet counts in peripheral blood. In addition, IL-11 accelerated reconstitution to normal range of myeloid progenitors from bone marrow and spleen of myelosuppressed mice. These data suggest that IL-11 may play an important role in the regulation of hematopoiesis, and the application of this novel cytokine may have clinical therapeutic benefits.

Animals↗
PubMed1993

Kinetic selectivity of cholinephosphotransferase in mouse liver: the Km for CDP-choline depends on diacylglycerol structure.

The effects of different 1,2-diacyl-sn-glycerols on the kinetic properties of CDP-choline:1,2-diacylglycerol cholinephosphotransferase (EC 2.7.8.2) from mouse liver microsomes have been studied. Initial-velocity experiments were carried out with various concentrations of several species of diacylglycerol at different fixed concentrations of CDP-choline. Kinetic analysis of these data showed a family of intersecting lines consistent with a sequential kinetic mechanism of catalysis. The Km and Vmax. values derived from rate data revealed a pronounced effect of diacylglycerol species utilization on the Km value for CDP-choline. There was a biphasic relationship between diacylglycerol chain length and the Km for CDP-choline. Substitution of an unsaturated fatty acid in the sn-2 position of distearin also dramatically increased the CDP-choline Km value as well as the Vmax. 1,2-Dipalmitoyl-sn-glycerol was the preferred substrate over other disaturated species, but 1,2-dihexanoyl-sn-glycerol could not be utilized. These results demonstrate the kinetic mechanism of in vitro catalysis and suggest a regulatory role for CDP-choline concentration in the diacylglycerol species selectivity of cholinephosphotransferase resulting in the de novo biosynthesis of different molecular species of phosphatidylcholine.

Animals↗
PubMed1993

Involvement of immediate-early gene expression in the synergistic effects of steel factor in combination with granulocyte-macrophage colony-stimulating factor or interleukin-3 on proliferation of a human factor-dependent cell line.

Steel factor (SLF) synergizes with granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) to stimulate proliferation of human factor-dependent cell line, MO7e. To elucidate molecular mechanisms underlying this synergism, induction of immediate-early genes was studied. Treatment of MO7e cells with SLF, GM-CSF, and IL-3 induced/enhanced expression of c-fos, junB, egr-1, and c-myc genes. SLF treatment of MO7e cells led to higher expression of c-fos, junB, and egr-1 genes than did treatment with GM-CSF or IL-3. However, GM-CSF and IL-3 had more prolonged effects on enhancement of the c-myc gene than SLF. Using optimal dosages for cell proliferation, induction of c-fos and junB was greater than additive with SLF plus GM-CSF or IL-3, as compared with each factor alone. Using suboptimal amounts of SLF with optimal GM-CSF or IL-3, induction of c-fos, junB, egr-1, and c-myc genes was greater than additive. De novo protein synthesis was not required for greater induction of these immediate-early genes by the combination of SLF plus GM-CSF. Based on nuclear run-on and actinomycin D experiments, the data suggest that the synergistic effects of SLF plus GM-CSF on the induction of immediate-early genes may be mediated in part at the level of transcription and mRNA stabilization for c-fos, at the level of mRNA stabilization for junB, and at the level of transcription for egr-1.

Cell Division↗
PubMed1993

Enrichment, characterization, and responsiveness of single primitive CD34 human umbilical cord blood hematopoietic progenitors with high proliferative and replating potential.

To characterize the growth of cord blood progenitor cells, single nonadherent, low-density, T-lymphocyte-depleted CD34 cells were sorted by flow cytometer with an autoclone device into single wells containing culture medium and cytokines. These cells were evaluated for proliferation and for replating ability of their progeny. This latter effect is used as a measure of self-renewal capacity. Colony formation was assessed in 1 degree wells containing various cytokines, alone and in combination, and single colonies deriving after 21 days in semisolid medium were replated into 2 degree wells in the presence of the combination of purified preparations of recombinant human steel factor (SF, a c-kit ligand), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), and erythropoietin (Epo). Replating of single colonies was performed also for 3 degrees, 4 degrees, and 5 degrees cultures. In the presence of serum, colony formation was observed in > 66% of the wells stimulated with the combination of Epo, SF, GM-CSF, G-CSF, and IL-3, and more than 39% of the colonies formed in these 1 degree wells were very large in size (> 2.5 mm in diameter, dense in the center, and containing > 10(4) cells/colony). The replating efficiency of these large colonies was up to 93% with generation of subsequent colonies of very large size. Replating could be shown for up to five generations. The cells in these colonies were large, nonspecific esterase positive, and contained large amounts of cytoplasm with one or more nuclei containing several nucleoli per nucleus. Smaller colonies (1 to 2.5 mm in diameter and dense in the center) containing similar cells and making up an additional 14% of the colonies formed in 1 degree wells also showed extensive replating capacity, including generation of larger colonies. These colony-forming cells are likely similar to the murine macrophage high-proliferative potential colony-forming cells. The cells giving rise to these colonies are present in about eightfold higher frequency in cord blood than in adult bone marrow. These cells may at least in part be associated with the successful hematopoietic repopulating capacity of umbilical cord blood cells.

Antigens, CD↗
PubMed1993

Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells.

Interleukin (IL)-7 has been evaluated for its influence, alone or in combination with local hyperthermia (LH), on B16a melanoma-bearing mice. Six- to eight-week-old C57BL/6J male mice were inoculated s.c. with 5 x 10(5) tumor cells into the left hind limb. Mice were randomly divided into four groups, and treated s.c. with IL-7 (5 ng) or saline as control, twice a day for three weeks beginning eight days after tumor inoculation. LH, using hot water circulator at 43 +/- 0.2 degrees C for 30 min, was induced to the limb with tumor twice a week for two weeks. Size of the primary tumor was measured every other day for five weeks. Mice were sacrificed five weeks after tumor inoculation. The size of the primary tumor and the number of lung metastases were reduced in mice treated either with IL-7 or LH alone. As a control for IL-7, granulocyte colony stimulating factor (G-CSF) alone had no effect on primary tumor size or number of lung metastases. The greatest antitumor effect was observed in mice treated with IL-7 in combination with LH. Survival was prolonged significantly only in mice treated with IL-7 plus LH compared with that of mice treated with saline. Decreased natural killer (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/Lyt2+ cells were associated with tumor growth. These parameters were restored in mice treated with IL-7 plus LH. Increases in levels of IL-1 alpha, IL-6, tumor necrosis factor (TNF alpha) and interferon (IFN gamma) were associated with an increase in the survival of tumor-bearing mice treated with IL-7 and/or LH. These results suggest that changes in T-cell, NK cell and cytokines such as IL-1 alpha, IL-6, TNF-alpha and IFN-gamma in response to IL7 and/or LH might account for prolonged survival of B16a melanoma-bearing mice and that IL-7 might be useful as a potential antitumor agent combined with other therapy in certain malignant solid tumors with metastases.

Animals↗
PubMed1993

Characterization of cord blood stem/progenitor cells.

Based on in vitro studies, umbilical-cord blood has been used clinically to engraft the hematopoietic systems of children. To evaluate the capacity of a single collection of cord blood to engraft an adult, it is important to consider not only the number, but also the quality of stem/progenitor cells in cord blood. We demonstrate that cord blood contains multipotential progenitor cells, possibly subsets of stem cells, that have extensive self-renewal capacity, as estimated by their capacity to form numerous secondary colonies of multiple lineages in secondary replates from single multipotential colonies. This replating capacity is enhanced by a factor or factors, perhaps novel, in cord blood plasma.

Cell Separation↗
PubMed1993

Haemopoietic stem/progenitor cell transplant in Fanconi anaemia using HLA-matched sibling umbilical cord blood cells.

There have only been a few reports documenting the use of umbilical cord blood as a source of stem cells for haemopoietic reconstitution. We report our experience with a child with Fanconi anaemia (FA) who underwent a stem cell transplant using umbilical cord blood cells from his HLA matched sibling. Although the engraftment was somewhat slow, it was complete and comparable to other transplants performed in FA patients using HLA matched sibling marrow. There was no graft-versus-host disease. The post-transplant period was uncomplicated and, at a follow-up of 36 months, this child is well with normal blood counts and immune function.

Child, Preschool↗
PubMed1993

Detection of human myeloid progenitor cells in a murine background.

Cell-mixing experiments were performed to determine whether human (hu) peripheral blood plasma would select for the growth of hu myeloid progenitor cells in vitro. Mixtures of hu male umbilical cord blood and murine (mu) female bone marrow (100% hu, 100% mu, 1.0% hu or 10% hu and 50% hu) were plated in methylcellulose cultures that contained either hu plasma or fetal bovine serum (FBS). Cultures were supplemented with recombinant (r) hu erythropoietin (Epo) alone or in combination with rhu granulocyte-macrophage colony stimulating factor (GM-CSF), rmuGM-CSF or rhu steel factor (SLF). DNA was extracted from day 14 colonies and clusters, and the polymerase chain reaction (PCR) was used to detect the hu Y-chromosome satellite DNA sequence. Results of these studies revealed that hu plasma used in combination with hu growth factors selected for the growth of hu progenitor cells. Mu cells grew in hu plasma only at high cell-plating concentrations. This selective effect was due to a heat labile factor or factors, since mu cells grew equally well in heat-inactivated hu plasma and FBS. Cells in individual progenitor cell colonies and clusters cultured in hu plasma contained hu Y-chromosome-specific DNA sequences that were detectable after PCR-mediated amplification, thus eliminating the need for time-consuming Southern transfer. This study describes a method whereby hu/immune-deficient mice can be screened rapidly for hu myeloid engraftment. These results also indicate that the hu identity of colonies and clusters cultured in hu plasma must be genetically confirmed, especially when hu cells may represent a low percentage of the total cells plated.

Animals↗
PubMed1993

Differential responses of myeloid progenitor cells from patients with myeloid leukemia and myelodysplasia to the costimulating effects of steel factor in vitro.

Steel factor (SLF, c-kit ligand), a potent costimulating cytokine in vitro for myeloid progenitor cells from normal donors, is currently being evaluated in clinical trials for effects on hematopoiesis. Based on a preliminary observation that colony-stimulating factor (CSF)-responsive myeloid progenitor cells (CFU-GM) from a few patients with acute myeloid leukemia (AML) did not respond to the costimulating effects of SLF, we evaluated responsiveness of bone marrow or blood CFU-GM from 26 patients with either AML, chronic myeloid leukemia (CML) or myelodysplastic syndrome (MDS) to the effects in vitro of SLF and/or granulocyte-macrophage CSF (GM-CSF). Cells from all 26 patients responded to the stimulating effects of GM-CSF, but marked heterogeneity was detected in each disease category to the costimulating effects of SLF. Nine of 13 patients with AML, 2 of 6 patients with CML and 4 of 7 patients with MDS had clonogenic cells that did not respond significantly to the costimulating effects of SLF. In a more limited study of cells from patients with MDS, it was noted that if the CFU-GM of that patient did not respond to SLF enhancement of CSF-induced colony formation, neither did the erythropoietin (Epo)-dependent erythroid (BFU-E) or multipotential (CFU-GEMM) cells of that patient (3 cases of refractory anemia [RA] evaluating bone marrow and in 1 case blood progenitors as well). If CFU-GM responded, BFU-E and CFU-GEMM responded (bone marrow from 1 patient with chronic myelomonocytic leukemia [CMMol]). Clinical criteria did not readily distinguish between patients who had SLF-responsive vs. -nonresponsive clonogenic cells. While the mechanistic reason for this heterogeneity in responsiveness is not clear, these differences should be carefully considered for possible clinical trials with SLF in patients with acute and chronic myeloid leukemia and MDS.

Adult↗
PubMed1993

Comparative effects of suppressive cytokines on isolated single CD34(3+) stem/progenitor cells from human bone marrow and umbilical cord blood plated with and without serum.

A number of cytokines have been implicated in the suppression of myeloid stem and progenitor cell proliferation. It has been suggested that some of these act directly on the stem/progenitors themselves, based on the effects of these cells, plated in culture at low seeding densities, on highly enriched populations. These studies, however, do not definitively rule out effects on accessory cells. To more rigorously evaluate direct-acting suppressive effects of cytokines, such cytokines were assessed for their effects on colony formation initiated by single bone marrow (BM) or umbilical cord blood (CB) CD34 cells sorted into single wells in the presence of a combination of growth-stimulating cytokines (erythropoietin [Epo], steel factor [SLF], granulocyte-macrophage colony-stimulating factor [GM-CSF], and interleukin-3 [IL-3]) and in the presence or absence of serum. Under these conditions, it was demonstrated that H-ferritin, transforming growth factor-beta 1 (TGF-beta 1), and members of the chemokine family (macrophage inflammatory protein-1 alpha [MIP-1 alpha], MIP-2 beta, platelet factor 4 [PF4], IL-8, and macrophage chemotactic and activating factor [MCAF]) had direct significant suppressive activities on single stem/progenitor cells from adult human BM in the presence or absence of serum. Single sorted CB cells were much less sensitive to inhibition by these cytokines. The reasons for this differential sensitivity are not known. Of possible relevance to this for cytokines, such as H-ferritin and the chemokines that have actions during S-phase of the cell cycle, CB progenitors were in slower cycle at initiation of culture than were BM progenitors.

Antigens, CD↗
PubMed1993

Characterization of interleukin-7-induced changes in tyrosine phosphorylation and c-myc gene expression in normal human T cells.

Interleukin-7 (IL-7) is a growth factor involved in regulating lymphopoiesis. We have chosen to study the signal transduction pathway of IL-7 in normal human peripheral blood T lymphocytes. Two early events that occur as a consequence of specific ligand-receptor interaction were examined: activation of protein tyrosine kinases and induction of primary response gene expression. Following treatment of human peripheral blood T cells with IL-7, four cellular proteins with relative molecular weights of 95- (doublet), 105-, and 130-kd were rapidly tyrosine phosphorylated as detected by immunoblotting with an antiphosphotyrosine monoclonal antibody (MAB). The 105-kd tyrosine-phosphorylated protein was membrane-associated after IL-7 stimulation. Treatment of human peripheral blood T cells with IL-7 enhanced expression of the primary response gene c-myc approximately three-fold, as detected by Northern blotting, in the presence or absence of protein synthesis. The rate of c-myc gene transcription increased in the presence of IL-7 and could account for the observed elevation of c-myc RNA levels. In addition, IL-7 treatment induced a slight increase in c-myc message stability. Experiments performed with the protein tyrosine kinase inhibitor genistein and the serine-threonine kinase inhibitor 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H-7) demonstrated that these kinases were required for IL-7 enhancement of c-myc expression. Treatment with tetradecanoyl phorbol acetate (TPA), a potent activator of protein kinase C (PKC), in combination with IL-7 induced a level of c-myc expression greater than that elicited by either factor alone, suggesting that TPA and IL-7 utilize cooperative signaling pathways to increase c-myc gene expression.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Cord blood banking for hematopoietic stem cell transplantation: an international cord blood transplant registry.

Human umbilical cord blood contains enough hematopoietic stem cells for transplantation instead of marrow cells to cure children and adults with leukemia and other potentially fatal marrow disorders. An international cord blood transplantation registry is currently collecting information about the results of these transplants. As a result of relative immune deficiency at birth, it is likely that partially matched unrelated transplants can be successful; for this purpose an international cord blood banking project is described.

Adult↗
PubMed1993

In vivo effects of purified recombinant human macrophage colony-stimulating factor in combination with local hyperthermia on tumor progression in B16a melanoma bearing mice.

Recombinant human (rhu) macrophage colony-stimulating factor (M-CSF) was evaluated, alone or in combination with local hyperthermia (LH), for their antitumor effects in mice inoculated with B16a melanoma cells. Several tumor related parameters and other hematopoietic and immunologic parameters were evaluated 5 weeks after subcutaneous (s.c.) inoculation of tumor cells into the right limbs of C57BL/6J male mice. RhuM-CSF was administered at 20 micrograms/injection, s.c., twice a day for 5 days/week for 2 weeks beginning 6 days after tumor cell inoculation and LH (43 +/- 0.2 degrees C) was given for 30 min twice/week for 2 weeks. Combined therapy prolonged survival of mice and caused significant inhibition of tumor growth, as measured by the volume or size of primary tumor, number and size of lung metastases, and chromatin fragment (CF) formation in tumor bearing mice, while treatment with M-CSF or LH alone had less or no effect. Combined therapy also resulted in increased numbers of splenic T-lymphocytes and the ratio of T-helper/suppressor cells, restoration of natural killer (NK) cell activity, increased numbers of peritoneal macrophages and their erythrophagocytosis capacity, and increased release or production of tumor necrosis factor (TNF)-alpha, but not interleukin (IL)-1 alpha or IL-6. These results add to previous evidence that M-CSF might be a relevant therapeutic agent in combination with other therapies in the treatment of certain malignant diseases.

Animals↗