1.Plasma G-CSF and GM-CSF Concentrations and Expression of their Receptors on the Granulocyte in Children with Leukocytosis.
Won Seok CHOI ; Kyung Hwan RYU ; You Jeong KIM ; So Young KIM ; Hyun Hee KIM ; Wonbae LEE
Journal of the Korean Pediatric Society 2003;46(3):271-276
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
2.Plasma G-CSF and GM-CSF Concentration and Amount of Their Receptors on the Granulocyte in Kawasaki Disease.
Young Kyoung YOO ; Gibum LEE ; Hyun Hee KIM ; Soo Young KIM ; You Jeong KIM ; Wonbae LEE
Journal of the Korean Pediatric Society 2003;46(4):376-381
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
3.Serum amyloid A inhibits dendritic cell differentiation by suppressing GM-CSF receptor expression and signaling.
Ji Cheol KIM ; Young Su JUNG ; Ha Young LEE ; Joon Seong PARK ; Yoe Sik BAE
Experimental & Molecular Medicine 2017;49(8):e369-
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
4.Quantities of Receptor Molecules for Colony Stimulating Factors on Leukocytes in Measles.
You Jeong KIM ; So Young KIM ; Young Yoo KIM ; Jong Wan KIM ; Je Hoon LEE ; Kyung Ja HAN ; Won Bae LEE
Yonsei Medical Journal 2002;43(1):43-47
We analyzed the comparative amounts of granulocyte-colony stimulating factor (G-CSFr) and granulocyte macrophage CSF (GM-CSFr) receptors expressed on neutrophils and monocytes in measles patients to investigate the role of these CSFrs in the development of leukopenia including neutropenia and monocytopenia in measles. EDTA-anticoagulated peripheral blood of 19 measles patients, 10 children with other infections showing leukopenia and 16 children with normal complete blood cell counts (CBC)s were analyzed using flow cytometry and QuantiBRITE. The leukocyte (5260 +/- 2030/uL vs. 9900 + 2680/uL, p=0.000), neutrophil (2580 +/- 960/uL vs. 4250 +/- 2750/uL, p=0.024) and the lymphocyte counts of measles patients (1810 +/- 1430/uL vs. 4530 +/- 3450/uL, p= 0.006) were lower than in the normal controls. The neutrophils of measles patients expressed similar amounts of G- CSFr (1858 +/- 355) as normal children (1764 +/- 477, p= 0.564) and leukopenic patients (1773 +/- 673, p=0.713), but lower levels of GM-CSFr (535 +/- 118) than normal children (957 +/- 344, p=0.000) and leukopenic patients (832 +/- 294, p=0.002). The monocytes of measles patients expressed similar amounts of G-CSFr (916 +/- 336) and GM-CSFr (3718 +/- 906) as normal children (1013 +/- 391 and 4125 (2645, p > 0.05) but less than leukopenic patients (1454 +/- 398 and 5388 +/- 806, p > 0.05). The neutrophil and monocyte counts of measles patients did not correlate with the amount of G-CSFr or GM-CSFr expressed on neutrophils or monocytes (p > 0.05), but in the normal children, the monocyte count correlated with the levels of GM-CSFr on monocytes (r=0.951, p=0.049). In conclusion, neutropenia is one of the more important characteristics of measles patients, which could be due to the decreased GM-CSFr expression on neutrophils. However, the monocytopenia found in measles patients is not due to the decreased expression of CSFr on the monocytes.
Human
;
Leukocyte Count
;
Measles/*blood
;
Monocytes/*chemistry
;
Neutropenia/etiology
;
Neutrophils/*chemistry
;
Receptors, Granulocyte Colony-Stimulating Factor/*blood
;
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/*blood
5.Inhibition of Fungi-Induced Nasal Polyp Epithelial Cells Activation by Corticosteroids.
Journal of Rhinology 2006;13(1):32-36
BACKGROUND AND OBJECTIVES: Airway epithelial cells contribute to the pathogenesis of air disease by their interaction with inhalant pathogenic extracts. Airborne fungi interact with nasal epithelial cell and enhance the production of inflammatory cytokines. Glucocorticosteroids (GCs) have been used therapeutically for nasal polyps and allergic disease with potent anti-inflammatory effects. The purpose of this study was to investigate the inhibitory effect of GCs on fungi induced nasal epithelial cell activation. MATERIALS AND METHODS: The epithelial cells of nasal polyps were obtained from patients and stimulated with Alternaria. To evaluate the anti-inflammatory effects of GCs, Alternaria was pretreated with GCs (triamcinolone, dexamethasone, and budesonide) and cultured with epithelial cells. Interleukin-8 (IL-8) and granulocyte-macrophage colony stimulating factor (GM-CSF) were measured to determine the activation of epithelial cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) test for protease-activated receptors (PARs) mRNA expression in nasal epithelial cells were performed. RESULTS: Alternaria enhanced the production of IL-8 and GM-CSF from nasal epithelial cells. GCs inhibited the activation of nasal epithelial cells, but the PAR2 and PAR3 mRNA expression were not suppressed by GCs. CONCLUSION: These data suggest that GCs inhibit the production of chemical mediators by Alternaria, but anti-inflammatory effect of GCs are not associated with PARs.
Adrenal Cortex Hormones*
;
Alternaria
;
Colony-Stimulating Factors
;
Cytokines
;
Dexamethasone
;
Epithelial Cells*
;
Fungi
;
Granulocyte-Macrophage Colony-Stimulating Factor
;
Humans
;
Interleukin-8
;
Nasal Polyps*
;
Receptors, Proteinase-Activated
;
RNA, Messenger
6.Modulation of expression of human GM-CSF and GM-CSFRalpha by total saponins of Panax ginseng.
Sha-Li WANG ; Di CHEN ; Ya-Ping WANG ; Yong-Gang LIU ; Rong JIANG
Acta Physiologica Sinica 2003;55(4):487-492
The purpose of the present study was to investigate the biological mechanism for modulating granulocytopoiesis by Panax ginseng. The techniques of culture of hematopoietic progenitor cells and hematopoietic stromal cells in vitro, biological assay of hematopoietic growth factor (HGF), immunocytochemistry, in situ hybridization of nucleic acid, immunoprecipitation and Western blot were used to explore the effect of total saponins of Panax ginseng (TSPG) on the expression of human granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte-macrophage colony stimulating factor receptor alpha (GM-CSFRalpha). The results indicated that (1) bone marrow stromal cell (BMSC), thymocyte (TC), splenocyte (SC), endothelial cells (EC), and monocyte (MO) conditioned media prepared with TSPG (50 microg/ml) could significantly enhance the proliferation of CFU-GM; (2) the expressions of GM-CSF in protein and mRNA level in BMSC, TC, SC, EC and MO induced by TSPG (50 microg/ml) were much higher than that of the control; (3) the expression of GM-CSFRalpha protein in hematopoietic cells induced by TSPG (50 microg/ml) was stronger than that of the control; (4) TSPG (50 microg/ml) could stimulate the transient tyrosine phosphorylation of GM-CSFR and Shc protein. We speculate that TSPG may directly and/or indirectly promote the stromal cells and lymphocytes to produce GM-CSF and other cytokine and induce bone marrow hematopoietic cells to express GM-CSF receptors (GM-CSFRalpha), leading to the regulation of the GM-CSFR-mediated signals transduction pathway and the proliferation of human CFU-GM.
Bone Marrow Cells
;
cytology
;
metabolism
;
Cells, Cultured
;
Granulocyte-Macrophage Colony-Stimulating Factor
;
metabolism
;
Hematopoietic Stem Cells
;
cytology
;
metabolism
;
Humans
;
Panax
;
chemistry
;
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
;
metabolism
;
Saponins
;
isolation & purification
;
pharmacology
;
Signal Transduction
;
Stromal Cells
;
cytology
;
metabolism
7.Expression of G-CSF and GM-CSF receptors on CD34 positive cells in aplastic anemia and myelodysplastic syndrome patients and its significance.
Hong-Zhi XU ; Ai LI ; Yuan YU ; Jian-Feng LI ; Xin LIU ; Xiang-Hua WANG ; Xin WANG ; Gong-Li XU
Journal of Experimental Hematology 2008;16(6):1308-1311
This study was aimed to detect the ratio of CD34+ cells in bone marrow mononuclear cells (BMMNCs) and the expression rate of G(M)-CSFR on CD34+ cells in bone marrow of the patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). The ratio of CD34+ cells in BMMNCs and the expression rate of G(M)-CSFR on cells of 27 AA patients, 45 MDS patients and 20 controls were detected by flow cytometry (FCM). The results showed that the ratio of CD34+ cells in BMMNCs of AA patients reduced and was significantly different from controls (p<0.05), the ratio of CD34+ cells in MDS patients elevated and was significantly different from controls (p<0.05). Compared with controls and MDS-RA patients, the ratio of CD34+ cells in MDS-RAEB patients significantly elevated (p<0.05), but there was no significant difference between MDS-RA patients and controls (p>0.05). The ratio of CD34+ cells in MDS-RA patients was significantly higher than that in AA patients (p<0.05). There was no significant difference in expression rate of G-CSFR on CD34+ cells between AA patients and controls, MDS patients and controls, AA patients and MDS patients, MDS-RA patients and MDS-RAEB patients (p>0.05). The expression rate of GM-CSFR in MDS patients was significantly higher than that in AA patients and controls (p<0.05), but there was no significant difference between AA patients and controls, MDS-RA patients and MDS-RAEB patients (p>0.05). In AA patients, the ratio of CD34+ cells in BMMNCs was less than 0.1% accounts for 6/8 SAA patients, compared with 2/19 in CAA (p<0.05). There was no correlation between the expression rate of either G-CSFR or GM-CSFR and neutrophil count at diagnosis (r=0.058 and r=0.044). In MDS patients, there was no correlation between bone marrow CD34+ cells ratio and peripheral neutrophil count at diagnosis (r=-0.335). And there was no correlation between the expression of either G-CSFR or GM-CSFR and neutrophil count on diagnosis (r=0.064 and r=0.051). It is concluded the detection of CD34+ cells and their surface expression rate of G(M)-CSFR in AA and MDS is useful in diagnosis and differential diagnosis of these two diseases.
Adult
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Anemia, Aplastic
;
metabolism
;
Antigens, CD34
;
immunology
;
Bone Marrow Cells
;
cytology
;
immunology
;
metabolism
;
Case-Control Studies
;
Female
;
Flow Cytometry
;
Humans
;
Male
;
Middle Aged
;
Myelodysplastic Syndromes
;
metabolism
;
Receptors, Granulocyte Colony-Stimulating Factor
;
metabolism
;
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
;
metabolism
8.Varying expression levels of colony stimulating factor receptors in disease states and different leukocytes.
Kyo Young LEE ; Byung Gyu SUH ; Jong Wan KIM ; Won Bae LEE ; So Young KIM ; Young Yoo KIM ; Je Hoon LEE ; Ji Hyang LIM ; Myung Shin LIM ; Chang Suk KANG ; Kyung Ja HAN
Experimental & Molecular Medicine 2000;32(4):210-215
Administration of G-CSF may not always respond in rise of neutrophil counts in different patient population. In order to understand a possible inter-relationship between the G-CSF and GM-CSF induced leukocyte responses and expression levels of receptors for G-CSF (G-CSFr) and GM-CSF (GM-CSFr), the levels of each receptor and CSF were measured in patients with basophilia (8), eosinophilia (14) and bacterial infection showing neutrophilia (12) in comparison with normal healthy adults (12) and children (14). G-CSFr was expressed in neutrophils in the largest amount followed by monocytes, but GM-CSFr was expressed more in monocytes than neutrophils. Lymphocytes and basophils did not express G-CSFr or GM-CSFr. The amount of GM-CSFr in neutrophils was present less in patients with infection than normal control (P = 0.031). The neutrophils expressed more G-CSFr than GM-CSFr. The quantity of G-CSFr in eosinophil showed marked interval change, higher in acute stage. The plasma concentrations of G-CSF in patients with infection were much higher than normal adults or children (117.95 +/- 181.16 pg/ml, P < 0.05). Binding assay with excess amount of CSFs could discriminate the patient who did not show any response to G-CSF or GM-CSF administration. After incubation with excess CSFs, more receptors were blocked in children than in adults (G-CSF P = 0.024, GM-CSF P = 0.006). These results indicate that the amount of CSFr in leukocyte varies in different types of leukocyte, and changes according to the patients' condition even in the same type of leukocyte, and the CSFrs of children bind to CSFs more than those of adults.
Adult
;
*Bacterial Infections
;
Basophils/chemistry
;
Breast Neoplasms
;
Child
;
Colony-Stimulating Factors/*blood
;
Eosinophilia
;
Human
;
Leukemia, Myeloid, Chronic
;
*Leukocyte Disorders
;
Monocytes/chemistry
;
*Neoplasms
;
Neutrophils/chemistry
;
Receptors, Colony-Stimulating Factor/*analysis
;
Receptors, Granulocyte Colony-Stimulating Factor/analysis
;
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/analysis
9.The Prostaglandin E Receptor Agonists Increase Granulocyte Macrophage Colony-Stimulating Factor in Prostate Cancer Cells.
Tae Hyoung KIM ; Young Sun KIM ; Soon Chul MYUNG ; Doo Hyung LEE ; Eun Ha WON ; Shin Young LEE
Korean Journal of Urology 2004;45(12):1272-1278
PURPOSE: The predilection for prostate carcinoma cells to metastasize to bone suggests the hypothesis that bone and/or bone marrow-derived factors may promote prostate carcinoma cell growth and/or their survival. To date, little work has been performed to characterize the nature of granulocyte macrophage colony-stimulating factor (GM-CSF) and the expression of prostaglandin E2 receptors (EPs) in prostate cancer (PC) cells. The aim of this study is to evaluate the effects of GM-CSF on cell proliferation and the effects of EP agonists on the production of GM-CSF in the PC-3 cells. MATERIALS AND METHODS: The bone-derived PC-3 cell line was used in this study. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the mRNA expression of EP1, 2, 3 and 4 and hGM- CSF. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was done to estimate the viability of PC-3 cells after hGM-CSF treatment. hGM-CSF was measured by enzyme-linked immunosorbent assay (ELISA) after treatments with the EPs agonist at 10(-10), 10(-8), 10(-6)M, respectively. RESULTS: EP2, 3 and 4 and hGM-CSF were expressed in the PC-3 cell line. Viability of the PC-3 cells was significantly increased by hGM-CSF administration in a dose- and time-dependent manner. Also, our data indicated that EP2, 3 and especially 4 agonists induced a significant dose- dependent increase in hGM-CSF production in comparison to the control group in the conditioned ELISA medium. CONCLUSIONS: These results suggest that GM-CSF may be part of a network of an autocrine-regulatory loop system that modulates the biologic activity of prostate carcinoma cells. Our data suggest that GM-CSF and EPs may represent a possible novel therapeutic target that manipulates the proliferative rate of prostate tumors.
Cell Line
;
Cell Proliferation
;
Cyclooxygenase 2
;
Dinoprostone
;
Enzyme-Linked Immunosorbent Assay
;
Granulocyte-Macrophage Colony-Stimulating Factor
;
Granulocytes*
;
Macrophage Colony-Stimulating Factor*
;
Macrophages*
;
Polymerase Chain Reaction
;
Prostate*
;
Prostatic Neoplasms*
;
Receptors, Prostaglandin E*
;
Reverse Transcription
;
RNA, Messenger
10.The Prostaglandin E Receptor Agonists Increase Granulocyte Macrophage Colony-Stimulating Factor in Prostate Cancer Cells.
Tae Hyoung KIM ; Young Sun KIM ; Soon Chul MYUNG ; Doo Hyung LEE ; Eun Ha WON ; Shin Young LEE
Korean Journal of Urology 2004;45(12):1272-1278
PURPOSE: The predilection for prostate carcinoma cells to metastasize to bone suggests the hypothesis that bone and/or bone marrow-derived factors may promote prostate carcinoma cell growth and/or their survival. To date, little work has been performed to characterize the nature of granulocyte macrophage colony-stimulating factor (GM-CSF) and the expression of prostaglandin E2 receptors (EPs) in prostate cancer (PC) cells. The aim of this study is to evaluate the effects of GM-CSF on cell proliferation and the effects of EP agonists on the production of GM-CSF in the PC-3 cells. MATERIALS AND METHODS: The bone-derived PC-3 cell line was used in this study. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the mRNA expression of EP1, 2, 3 and 4 and hGM- CSF. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was done to estimate the viability of PC-3 cells after hGM-CSF treatment. hGM-CSF was measured by enzyme-linked immunosorbent assay (ELISA) after treatments with the EPs agonist at 10(-10), 10(-8), 10(-6)M, respectively. RESULTS: EP2, 3 and 4 and hGM-CSF were expressed in the PC-3 cell line. Viability of the PC-3 cells was significantly increased by hGM-CSF administration in a dose- and time-dependent manner. Also, our data indicated that EP2, 3 and especially 4 agonists induced a significant dose- dependent increase in hGM-CSF production in comparison to the control group in the conditioned ELISA medium. CONCLUSIONS: These results suggest that GM-CSF may be part of a network of an autocrine-regulatory loop system that modulates the biologic activity of prostate carcinoma cells. Our data suggest that GM-CSF and EPs may represent a possible novel therapeutic target that manipulates the proliferative rate of prostate tumors.
Cell Line
;
Cell Proliferation
;
Cyclooxygenase 2
;
Dinoprostone
;
Enzyme-Linked Immunosorbent Assay
;
Granulocyte-Macrophage Colony-Stimulating Factor
;
Granulocytes*
;
Macrophage Colony-Stimulating Factor*
;
Macrophages*
;
Polymerase Chain Reaction
;
Prostate*
;
Prostatic Neoplasms*
;
Receptors, Prostaglandin E*
;
Reverse Transcription
;
RNA, Messenger