No abstract available.
Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes* ; Humans* ; Macrophages* ; Methotrexate*

PURPOSE: This study aimed to demonstrate the possible pathogenesis of granulopoiesis in patients of Kawasaki disease(KD) using quantitative analysis of G-CSF, GM-CSF and their CSFr. METHODS: The plasma levels of G-CSF, GM-CSF, G-CSFr and GM-CSFr were studied in 14 patients in the acute phase of KD; 13 children with normal peripheral white blood cell counts were used as the normal control group. The plasma concentration of G-CSF, GM-CSF were analyzed by ELISA. The G-CSFr and GM-CSFr on the peripheral granulocytes were analyzed by a quantitative flow cytometric assay and QuantiBRITE, and the quantitative changes of receptors which did not combine with G-CSF and GM-CSF were measured. RESULTS: The total number of leukocytes in KD was similar to normal control group, but the leukocytes increased according to the number of neutrophils. The plasma concentration of G-CSF were decreased similar to normal control group(P=0.133), but that of GM-CSF decreased more than the normal control group(P=0.227). The quantity of G-CSFr, GM-CSFr were revealed to be no less than the normal control(P=0.721, P=0.912). After incubation with excessive G-CSF, the expressed G-CSFr on the neutrophils were decreased in both groups(P=0.554). The quantities of expressions of GM- CSFr on the neutrophil after incubation with the excessive GM-CSF were always increased in both groups(P=0.255). The amount of GM-CSFr of neutrophils are in proportion to total white blood cells (r=0.788, P=0.035), but it wasn't in the case of KD(P=0.644). CONCLUSION: The leukocytosis in KD that mediated by increasing neutrophil was not correlated with the plasma concentrations of G-CSF and GM-CSF, and the amount of expression of G-CSFr and GM-CSFr on granulocyte. It is possible that the reduction of concentration of GM-CSF results by increasing the active GM-CSFr.
Child ; Enzyme-Linked Immunosorbent Assay ; Granulocyte Colony-Stimulating Factor* ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes* ; Humans ; Leukocyte Count ; Leukocytes ; Leukocytosis ; Mucocutaneous Lymph Node Syndrome* ; Neutrophils ; Plasma* ; Receptors, Granulocyte Colony-Stimulating Factor ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

PURPOSE: Granulocyte-colony stimulating factor(G-CSF) and granulocyte macrophage-colony stimulating factor(GM-CSF) are principal cytokines in granulopoiesis and their physiologic effects are mediated through binding to specific cell surface receptors. Although it is known that the level of serum G-CSF and GM-CSF, and presentation of the receptors are increased in infectious diseases, there have been no studies to find the correlation between the granulopoiesis and leukocytosis. This study was designed to measure G-CSF and GM-CSF in leukocytosis and in control and to demonstrate the possible pathogenesis of granulopoiesis in leukocytosis using quantitative analysis of G- CSF, GM-CSF and their CSFr. METHODS: The plasma levels of G-CSF, GM-CSF of 13 children without leukocytosis and 14 children with leukocytosis were measured. Counts of cell surface G-CSFr and GM-CSFr were measured by combining anti G-CSFr and anti GM-CSFr monoclonal antibodies to their respective receptors by using quantitative flow cytometric assay. RESULTS: There was no significant difference betweeen the plasma concentration of G-CSF and GM-CSF in acute leukocytosis and in the control group. However, levels of G-CSFr in acute leukocytosis decreased significantly compared to the control(P=0.012) and the levels of GM-CSFr in both groups revealed no significant difference. CONCLUSION: Increase in the number of leukocyte in leukocytosis was mediated by increasing the number of neutrophil, and increased plasma concentration of G-CSF may be the cause of neutrophilia. But GM-CSF did not have any influence on leukocytosis.
Antibodies, Monoclonal ; Child* ; Communicable Diseases ; Cytokines ; Granulocyte Colony-Stimulating Factor* ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes* ; Humans ; Leukocytes ; Leukocytosis* ; Neutrophils ; Plasma* ; Receptors, Cell Surface ; Receptors, Granulocyte Colony-Stimulating Factor ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

OBJECTIVE: To investigate the influence of granulocyte colony stimulating factor (G-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF) on preimplantation development and implantation in mouse embryos. MATERIAL AND METHODS: Eight-cell stage mouse embryos were cultured for 96 hours with G-CSF or GM-CSF at concentrations of 10 pg/ml, 100 pg/ml, 1 ng/ml and 10 ng/ml. Embryos not treated with G-CSF or GM-CSF were served as control. The percentages of embryos which developed to expanded, hatched blastocyst stage and in vitro implantation at 96 hours were determined. Results were analyzed with Kolmogorov-Smirnov test and analysis of variance (ANOVA). The statistical significance was defined as p<0.05. RESULTS: The percentages of fully expanded blastocysts in all G-CSF and GM-CSF treatment groups were not significantly different from the control. The percentages of hatched blastocysts were significantly higher in 100 pg/ml and 10 ng/ml of G-CSF treatment group compared to the control (p<0.05, p<0.05, respectively). The percentages of hatched blastocysts were significantly lower in 1 ng/ml of GM-CSF treatment group compared to the control, 10 pg/ml, and 100 pg/ml of GM-CSF treatment group (p<0.05, p<0.05, p<0.05, respectively), and the percentages of hatched blastocysts were also significantly lower in 10 ng/ml of GM-CSF treatment group compared to the control and 100 pg/ml of GM-CSF treatment group (p<0.05, p<0.05, respectively). The percentages of implanted blastocysts in vitro were significantly higher following incubation with all concentrations of G-CSF compared to the control and, especially in 100 pg/ml and 10 ng/ml of G-CSF treatment groups compared to the control and other treatment groups. The percentages of implanted blastocysts in vitro were significantly higher in 10 pg/ml of GM-CSF treatment group than the control and 100 pg/ml of GM-CSF treatment groups (p<0.05, p<0.05, respectively). CONCLUSION: G-CSF and GM-CSF might influence on embryonic development and implantation in mouse embryos.
Animals ; Blastocyst ; Colony-Stimulating Factors* ; Embryonic Development ; Embryonic Structures* ; Female ; Granulocyte Colony-Stimulating Factor ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes* ; Mice* ; Pregnancy

BACKGROUND: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. METHODS: A carcinogen- induced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with gamma-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. RESULTS: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with gamma-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. CONCLUSION: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by gamma-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.
Animals ; Apoptosis ; Colony-Stimulating Factors* ; Colorectal Neoplasms ; Granulocyte-Macrophage Colony-Stimulating Factor ; Mice ; Mitomycin ; Vaccination ; Vaccines ; Zidovudine

Granulocyte macrophage-colony stimulating factor (GM-CSF) occupies a central position in the regulation of hematopoietic responses. GM-CSF not only signals proliferations of granulocyte-macrophage but also drives these cells into differentiation and activates mature cells of the GM-CSF sensitive lineage. Myelosuppression that is induced by M-VAC (methotrexate, vinblastine, doxorubicin, cisplatinum) chemotherapy brings many problems in successful treatment such as sepsis, dose reduction, delaying the schedule. Granulocyte-macrophage colony stimulating factor is introduced hopefully as a new solution for these problems. So we evaluated the efficacy and safety of GM-CSF in leukopenia induced by M-VAC chemotherapy in patients with urothelial cancer. GM-CSF was administered at 200ug subcutaneously in 10 M-VAC cycles of 6 patients on 5th and 6th day after M-VAC therapy. Sixteen cycles, by which only M-VAC chemotherapy was administered without GM-CSF. of the other 6 patients served as control group. Mean white blood cell count in peripheral blood at M-VAC 2nd day and 15th day was 5,630/mm3 and 4,240/mm3 in GM-CSF administered cycles, 6,58l/mm3and 3,613/mm3 in non GM-CSF administered cycles. There was no delayed cycle in administration of MTX and vinblastine at M-VAC 15th day in the cycles with GM-CSF. There was no significant side effects caused by GM- CSF. The result indicates that GM-CSF can be used safely and effectively against leukopenia after M-VAC chemotherapy of urothelial cancer.
Appointments and Schedules ; Colony-Stimulating Factors ; Doxorubicin ; Drug Therapy* ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Granulocytes ; Humans ; Leukocyte Count ; Leukopenia* ; Sepsis ; Vinblastine

In this study, we report that an acute phase reactant, serum amyloid A (SAA), strongly inhibits dendritic cell differentiation induced by GM-CSF plus IL-4. SAA markedly decreased the expression of MHCII and CD11c. Moreover, SAA decreased cell surface GM-CSF receptor expression. SAA also decreased the expression of PU.1 and C/EBPα, which play roles in the expression of GM-CSF receptor. This inhibitory response by SAA is partly mediated by the well-known SAA receptors, Toll-like receptor 2 and formyl peptide receptor 2. Taken together, we suggest a novel insight into the inhibitory role of SAA in dendritic cell differentiation.
Dendritic Cells* ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Interleukin-4 ; Receptors, Formyl Peptide ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor* ; Serum Amyloid A Protein* ; Toll-Like Receptors

PURPOSE: Antitumor effect of granulocyte macrophage colony-stimulating factor (GM-CSF)- producing murine colon cancer cells was elucidated against intrahepatic challenge of parental cancer cells, which is clinically relevant tumor model. MATERIALS AND METHODS: Using a model of liver metastasis by intrahepatic challenge of CT-26 murine colon carcinoma cells to syngeneic BALB/c mice, GM-CSF producing cells were given as a intradermal vaccine either 14 days prior to hepatic challenge, or in animals with established tumors. Tumor volume and survival were determined. RESULTS: Animals receiving vaccination showed significant systemic protection against the hepatic challenge of parental tumor cells, and in animals with established hepatic tumors significant response was observed with some prolongation in survival. CONCLUSION: It is concluded that GM-CSF-producing autologous tumor vaccine was effective for the protection of host agaisnt the metastatic hepatic tumor model. Even though its efficacy against the established tumor was not as significant as in protection, GM-CSF producing autologous tumor vaccine can provide support for the specific immunotherapy for the metastatic liver cancer.
Animals ; Colon ; Colonic Neoplasms ; Granulocyte-Macrophage Colony-Stimulating Factor ; Granulocytes ; Humans ; Immunotherapy* ; Liver ; Liver Neoplasms* ; Macrophage Colony-Stimulating Factor ; Mice ; Neoplasm Metastasis ; Parents ; Tumor Burden ; Vaccination

OBJECTIVETo explore the expression, characteristics and roles of macrophage colony-stimulating factor receptor (M-CSF-R) in human leukemia cell lines.

METHODSPeripheral blood mononuclear cells (PBMCs) collected from 3 healthy persons, cord blood mononuclear cells (CBMCs) collected from 5 healthy persons and 4 human myelomonocytic leukemia cell lines including J6-1, J6-2, K562 and HL-60 were studied by using ABC immunoperoxidaes assay, indirect immunofluorescene staining, flow cytometry, and Western blot.

RESULTSM-CSF-R was noticed to be localized in the cytoplasm, nucleus and at the membrane in 4 human leukemia cell lines; expression of M-CSF-R was not detected in normal human PBMCs without PHA stimulation. Human PBMCs stimulated by PHA expressed a low level of M-CSF-R. Frequencies of membrane bound M-CSF-R (M-CSF-mR) expression in J6-1, J6-2, K562 and HL-60 were 78.9%, 72.6%, 54.9% and 58.0% respectively. Frequencies of cytoplasm and nucleus associated M-CSF-R (M-CSF-cnR) were 52.3%, 44.3%, 28.0% and 65.3% respectively. One form of M-CSF-R with a molecular weight of 120 000 was detected both in the cytoplasm and nucleus of HL-60 cells. The half-life of M-CSF-cnR in leukemia cells mentioned above was longer than that of corresponding M-CSF-R in stimulated CBMCs, and the half-life of M-CSF-mR in leukemia cells was extended except that of M-CSF-mR in K562 cells. Both anti-M-CSF-R monoclonal antibody and recombinant human M-CSF soluble receptor could cause the growth arrest of HL-60 cell in G(0)/G(1) phase, and could inhibit the formation of colony of HL-60 cell in soft agarose.

CONCLUSIONSExpression of M-CSF-R in leukemia cells is heterogeneous. The accumulation of cellular M-CSF-R results in the low degradation rate of cellular M-CSF-R in leukemia cells, which could be a potential mitotic signal. Signal mediated by M-CSF-R is important and necessary for the growth of HL-60 cell.

Cell Line ; HL-60 Cells ; Humans ; Leukemia ; Leukocytes, Mononuclear ; metabolism ; Macrophage Colony-Stimulating Factor ; metabolism ; Receptor, Macrophage Colony-Stimulating Factor ; Tumor Cells, Cultured

Granulocyte-macrophage colony-stimulating factor (GM-CSF, also called CSF-2) is best known for its critical role in immune modulation and hematopoiesis. A large body of experimental evidence indicates that GM-CSF, which is frequently upregulated in multiple types of human cancers, effectively marks cancer cells with a ‘danger flag' for the immune system. In this context, most studies have focused on its function as an immunomodulator, namely its ability to stimulate dendritic cell (DC) maturation and monocyte/macrophage activity. However, recent studies have suggested that GM-CSF also promotes immune-independent tumor progression by supporting tumor microenvironments and stimulating tumor growth and metastasis. Although some studies have suggested that GM-CSF has inhibitory effects on tumor growth and metastasis, an even greater number of studies show that GM-CSF exerts stimulatory effects on tumor progression. In this review, we summarize a number of findings to provide the currently available information regarding the anticancer immune response of GM-CSG. We then discuss the potential roles of GM-CSF in the progression of multiple types of cancer to provide insights into some of the complexities of its clinical applications.
Dendritic Cells ; Granulocyte-Macrophage Colony-Stimulating Factor* ; Hematopoiesis ; Humans ; Immune System ; Neoplasm Metastasis ; Tumor Microenvironment