scholarly journals Prevention of experimental cerebral malaria by anticytokine antibodies. Interleukin 3 and granulocyte macrophage colony-stimulating factor are intermediates in increased tumor necrosis factor production and macrophage accumulation.

1988 ◽  
Vol 168 (4) ◽  
pp. 1499-1504 ◽  
Author(s):  
G E Grau ◽  
V Kindler ◽  
P F Piguet ◽  
P H Lambert ◽  
P Vassalli
Keyword(s):  
T Lymphocytes ◽  
Cerebral Malaria ◽  
Colony Stimulating Factor ◽  
Experimental Cerebral Malaria ◽  
Neurological Syndrome ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Macrophage Accumulation

IL-3 and granulocyte/macrophage colony stimulating factor (GM-CSF) are two cytokines released by activated T lymphocytes that stimulate the growth and differentiation of various hematopoietic cell lines, among which are macrophages. It has been shown that TNF/cachectin, another cytokine that is released mostly by activated macrophages, plays a central role in experimental cerebral malaria (CM), an acute and lethal neurological syndrome induced by Plasmodium berghei ANKA infection in CBA mice. Since CM requires functional CD4+ T lymphocytes to occur, we explored, by injecting rabbit antibodies to murine rIL-3 and/or GM-CSF, whether these cytokines are intermediates in the marked TNF release leading to CM. Treatment of infected mice with each antibody separately had no protective effect. In contrast, when both anti-rGM-CSF and anti-rIL-3 antibodies were injected together; (a) the occurrence of neurological syndrome was prevented in 90% of the cases; (b) the rise in serum TNF was prevented; and (c) macrophage accumulation in the spleen was significantly reduced. Murine CM appears to involve a cytokine cascade in which IL-3 and GM-CSF lead to the accumulation of TNF-releasing macrophages in vivo.

scholarly journals Direct effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on functional properties of human T lymphocytes

2018 ◽  
pp. 37-42
Author(s):  
Н.Д. Газатова ◽  
В.В. Малащенко ◽  
М.Е. Меняйло ◽  
О.Б. Мелащенко ◽  
Е.М. Морозова ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Interleukin 2 ◽  
Colony Stimulating Factor ◽  
High Concentration ◽  
Flow Cytofluorometry ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Актуальность. Исследовали прямые эффекты гранулоцит-макрофагального колониестимулирующего фактора (GM-CSF) человека на функциональную активность субпопуляций T-лимфоцитов. Методы. CD3+ Т-лимфоциты были выделены из крови здоровых доноров методом позитивной магнитной сепарации. T-клетки активировали частицами, конъюгированными с антителами (АТ) к молекулам CD3, СD28 и СD2 человека. Мембранную экспрессию CD3, CD4, СD45RA, СD197, CD25 и CD38 оценивали методом проточной цитофлюорометрии. Содержание интерферона- Результаты. Установлено, что GM-CSF в диапазоне концентраций 0,01-10,0 нг/мл не оказывал существенного влияния на содержание CD25+ клеток, среди активированных Т-лимфоцитов. Вместе с тем, GM-CSF в концентрации 0,1 и 1,0 нг/мл обладал способностью заметно увеличивать содержание CD38+ клеток среди наивных СD45RA+/СD197+ Т-клеток, а также среди СD45RA-/СD197+ Т-клеток центральной памяти, не оказывая при этом существенного влияния на экспрессию CD38, выявляемую среди эффекторных СD45RA-/СD197- и терминально дифференцированных СD45RA+/СD197- эффекторных Т-клеток. В относительно низкой концентрации (0,01 нг/мл) GM-CSF заметно снижал Т-клеточную продукцию INF-γ, тогда как в высокой концентрации (10,0 нг/мл) усиливал продукцию IL-2 и IL-4, снижая при этом выработку IL-10. Заключение. Полученные данные предполагают, что GM-CSF способен поддерживать активацию относительно низкодифференцированных Т-клеток, не оказывая при этом значимого влияния на активацию высоко дифференцированных Т-клеток. Background. We investigated direct effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the functionality of T-lymphocyte subsets. Methods. CD3 + T cells were isolated from the blood of healthy donors by positive magnetic separation. The isolated T cells were activated with particles conjugated with antibodies (Abs) to human CD3, CD28, and CD2 molecules. The membrane expression of CD3, CD4, СD45RA, СD197, CD25, and CD38 was evaluated by flow cytofluorometry. Contents of interferon-γ (IFN- γ), interleukin-2 (IL-2), IL-4, and IL-10 in culture supernatants were determined by the enzyme immunoassay. Results. GM-CSF at 0.01-10.0 ng/ml had no significant effect on the content of CD25+ cells among activated T lymphocytes. At the same time, GM-CSF at 0.1-1.0 ng/ml was able to noticeably increase the content of CD38+ cells among both naive CD45RA+/CD197+ T cells and central memory CD45RA-/CD197+ T cells without affecting the СD38 expression on effector CD45RA- /CD197- and terminally differentiated CD45RA +/ CD197- effector T cells. At a relatively low concentration (0.01 ng/ml), GM-CSF significantly decreased T-cell production of INF-γ whereas at a high concentration (10.0 ng/ml), GM-CSF detectably enhanced the secretion of IL-2 and IL-4 while lowering IL-10 production. Conclusion. The findings suggest that GM-CSF is capable of supporting the activation of relatively low-differentiated T cells without significantly affecting the activation of highly differentiated T cells.

The repeated sequence CATT(A/T) is required for granulocyte-macrophage colony-stimulating factor promoter activity

1990 ◽  
Vol 10 (11) ◽  
pp. 6084-6088
Author(s):  
S Nimer ◽  
J Fraser ◽  
J Richards ◽  
M Lynch ◽  
J Gasson
Keyword(s):  
T Lymphocytes ◽  
Promoter Activity ◽  
Repeated Sequence ◽  
Inducible Promoter ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Flanking Sequences ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The hematopoietic growth factor GM-CSF (granulocyte-macrophage colony-stimulating factor) is expressed by activated but not resting T lymphocytes. Previously, we localized GM-CSF-inducible promoter activity to a 90-bp region of GM-CSF 5'-flanking sequences extending from bp -53 to +37. To more precisely identify the GM-CSF DNA sequences required for inducible promoter activity in T lymphocytes, we have performed mutagenesis within a region of GM-CSF 5'-flanking sequences (bp -57 to -24) that contains the repeated sequence CATT(A/T). Mutations that do not alter the repeated CATT(A/T) sequence do not eliminate inducible promoter activity, whereas mutation or deletion of either of the CATT(A/T) repeats eliminates all inducible promoter activity in T-cell lines and in primary human T lymphocytes. Thus, both copies of the direct repeat CATT(A/T) are required for mitogen-inducible expression of GM-CSF in T cells.

scholarly journals The repeated sequence CATT(A/T) is required for granulocyte-macrophage colony-stimulating factor promoter activity.

1990 ◽  
Vol 10 (11) ◽  
pp. 6084-6088 ◽  
Author(s):  
S Nimer ◽  
J Fraser ◽  
J Richards ◽  
M Lynch ◽  
J Gasson
Keyword(s):  
T Lymphocytes ◽  
Promoter Activity ◽  
Repeated Sequence ◽  
Inducible Promoter ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Flanking Sequences ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The hematopoietic growth factor GM-CSF (granulocyte-macrophage colony-stimulating factor) is expressed by activated but not resting T lymphocytes. Previously, we localized GM-CSF-inducible promoter activity to a 90-bp region of GM-CSF 5'-flanking sequences extending from bp -53 to +37. To more precisely identify the GM-CSF DNA sequences required for inducible promoter activity in T lymphocytes, we have performed mutagenesis within a region of GM-CSF 5'-flanking sequences (bp -57 to -24) that contains the repeated sequence CATT(A/T). Mutations that do not alter the repeated CATT(A/T) sequence do not eliminate inducible promoter activity, whereas mutation or deletion of either of the CATT(A/T) repeats eliminates all inducible promoter activity in T-cell lines and in primary human T lymphocytes. Thus, both copies of the direct repeat CATT(A/T) are required for mitogen-inducible expression of GM-CSF in T cells.

scholarly journals Precursor frequency analysis of lymphokine-secreting alloreactive T lymphocytes. Dissociation of subsets producing interleukin 2, macrophage-activating factor, and granulocyte-macrophage colony-stimulating factor on the basis of Lyt-2 phenotype.

1982 ◽  
Vol 156 (5) ◽  
pp. 1366-1379 ◽  
Author(s):  
A Kelso ◽  
H R Macdonald
Keyword(s):  
T Lymphocytes ◽  
Interleukin 2 ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Average Production ◽  
Macrophage Colony Stimulating Factor ◽  
Precursor Frequency ◽  
Macrophage Colony ◽  
Almost All ◽  
Stimulating Factor

The frequencies of precursors of C57BL/6 T lymphocytes that respond to DBA/2 alloantigens by secreting the lymphokines interleukin 2 (IL-2), macrophage-activating factor (MAF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been directly compared with cytolytic T lymphocyte precursor (CTL-P) frequencies in limiting dilution microcultures established from spleen cells positively or negatively selected on the basis of Lyt-2 phenotype. A clear dichotomy was observed between CTL-P, which were contained in the Lyt-2+ fraction, and precursors of IL-2-secreting cells, which were detected almost exclusively in the Lyt-2- population. In contrast, precursors of cells secreting MAF and GM-CSF were found in both populations: almost all responding cells from the Lyt-2- fraction produced both these factors, whereas the precursor frequency of MAF-secreting and GM-CSF-secreting cells was three- to fourfold lower in the Lyt-2+ population. These frequency data were consistent with quantitative differences observed in the average production of these lymphokines by Lyt-2+ and Lyt-2- populations.

scholarly journals Direct effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on functional features of human T-lymphocytes

2018 ◽  
pp. 37-42
Author(s):  
Н.Д. Газатова ◽  
В.В. Малащенко ◽  
М.Е. Меняйло ◽  
В.А. Шмаров ◽  
О.Б. Мелащенко ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Interleukin 2 ◽  
Direct Effects ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Актуальность. Исследовали прямые эффекты гранулоцит-макрофагального колониестимулирующего фактора (GM-CSF) человека на функциональную активность субпопуляций T-лимфоцитов. Методы. CD3 Т-лимфоциты были выделены из крови здоровых доноров методом позитивной магнитной сепарации. T-клетки активировали частицами, конъюгированными с антителами (АТ) к молекулам CD3, СD28 и СD2 человека. Мембранную экспрессию CD3, СD4, СD45RA, СD197, CD25 и CD38 оценивали методом проточной цитофлюорометрии. Содержание интерферона-g (interferon-g, IFN-g), интерлейкина-2 (interleukin-2, IL-2). IL-4 и IL-10 в культуральных супернатантах определяли иммуноферментным методом. Результаты. Установлено, что GM-CSF в диапазоне концентраций 0,01-10,0 нг/мл не оказывал существенного влияния на содержание CD25 клеток, среди активированных Т-лимфоцитов. Вместе с тем, GM-CSF в концентрации 0,1-1,0 нг/мл обладал способностью заметно увеличивать содержание CD38 клеток среди наивных Т-клеток (СD45RA/СD197), а также среди Т-клеток центральной памяти (СD45RA/СD197), не оказывая при этом существенного влияния на экспрессию CD38, выявляемую среди эффекторных (СD45RA/СD197) и терминально дифференцированных (СD45RA/СD197) эффекторных Т-клеток. В относительно низкой концентрации (0,01 нг/мл) GM-CSF заметно снижал Т-клеточную продукцию INF-g, тогда как в высокой концентрации (10,0 нг/мл) усиливал продукцию IL-2 и IL-4, снижая при этом выработку IL-10. Заключение. Полученные данные позволяют предположить, что прямые эффекты GM-CSF на функциональную активность Т-клетки могут в значительной степени определяться как ее субпопуляционной принадлежностью, так и концентрацией цитокина в клеточном микроокружении. Background. We studied direct effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the function of T-lymphocyte subpopulations. Methods. CD3 T cells were isolated from the blood of healthy donors by positive magnetic separation. Isolated T cells were activated by particles conjugated with antibodies (Abs) to human CD3, CD28, and CD2 molecules. Membrane expression of CD4, СD45RA, СD197, CD25, and CD38 was evaluated by flow cytofluorometry. The contents of interferon-g (IFN-g), interleukin-2 (IL-2), IL-4, and IL-10 were determined in culture supernatants by the enzyme immunoassay. Results. GM-CSF at concentrations of 0.01-10.0 ng/ml had no significant impact on the content of CD25 cells among activated T lymphocytes. At the same time, GM-CSF at 0.1-1.0 ng/ml was able to noticeably increase the CD38 cell content among both naive CD45RA/CD197 T cells and central memory CD45RA/CD197 T cells, without significantly influencing the СD38 expression on effector CD45RA/CD197 and terminal-differentiated (CD45RA / CD197 effector T cells. GM-CSF at a relatively low concentration (0.01 ng/ml) significantly decreased T-cell production of INF-g whereas GM-CSF at a high concentration (10.0 ng/ml) detectably enhanced secretion of IL-2 and IL-4 and lowered IL-10 production. Conclusion. The results suggest that direct effects of GM-CSF on the T cell function could be largely determined by both its belonging to a subpopulation and the cytokine concentration in the cell microenvironment.

scholarly journals Cholesterol loading suppresses the atheroinflammatory gene polarization of human macrophages induced by colony stimulating factors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jani Lappalainen ◽  
Nicolas Yeung ◽  
Su D. Nguyen ◽  
Matti Jauhiainen ◽  
Petri T. Kovanen ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Foam Cells ◽  
Colony Stimulating Factor ◽  
Human Macrophages ◽  
Gm Csf ◽  
Macrophage Subpopulations ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

AbstractIn atherosclerotic lesions, blood-derived monocytes differentiate into distinct macrophage subpopulations, and further into cholesterol-filled foam cells under a complex milieu of cytokines, which also contains macrophage-colony stimulating factor (M-CSF) and granulocyte–macrophage-colony stimulating factor (GM-CSF). Here we generated human macrophages in the presence of either M-CSF or GM-CSF to obtain M-MØ and GM-MØ, respectively. The macrophages were converted into cholesterol-loaded foam cells by incubating them with acetyl-LDL, and their atheroinflammatory gene expression profiles were then assessed. Compared with GM-MØ, the M-MØ expressed higher levels of CD36, SRA1, and ACAT1, and also exhibited a greater ability to take up acetyl-LDL, esterify cholesterol, and become converted to foam cells. M-MØ foam cells expressed higher levels of ABCA1 and ABCG1, and, correspondingly, exhibited higher rates of cholesterol efflux to apoA-I and HDL2. Cholesterol loading of M-MØ strongly suppressed the high baseline expression of CCL2, whereas in GM-MØ the low baseline expression CCL2 remained unchanged during cholesterol loading. The expression of TNFA, IL1B, and CXCL8 were reduced in LPS-activated macrophage foam cells of either subtype. In summary, cholesterol loading converged the CSF-dependent expression of key genes related to intracellular cholesterol balance and inflammation. These findings suggest that transformation of CSF-polarized macrophages into foam cells may reduce their atheroinflammatory potential in atherogenesis.

The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor β- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns

Neonatology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Verena Schulte ◽  
Alexandra Sipol ◽  
Stefan Burdach ◽  
Esther Rieger-Fackeldey
Keyword(s):  
Respiratory Failure ◽  
Peripheral Blood ◽  
Colony Stimulating Factor ◽  
Term Infants ◽  
Respiratory Impairment ◽  
Gm Csf ◽  
A Subunit ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

<b><i>Background:</i></b> The granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays an important role in surfactant homeostasis. β<sub>C</sub> is a subunit of the GM-CSF receptor (GM-CSF-R), and its activation mediates surfactant catabolism in the lung. β<sub>IT</sub> is a physiological, truncated isoform of β<sub>C</sub> and is known to act as physiological inhibitor of β<sub>C</sub>. <b><i>Objective:</i></b> The aim of this study was to determine the ratio of β<sub>IT</sub> and β<sub>C</sub> in the peripheral blood of newborns and its association with the degree of respiratory failure at birth. <b><i>Methods:</i></b> We conducted a prospective cohort study in newborns with various degrees of respiratory impairment at birth. Respiratory status was assessed by a score ranging from no respiratory impairment (0) to invasive respiratory support (3). β<sub>IT</sub> and β<sub>C</sub> expression were determined in peripheral blood cells by real-time PCR. β<sub>IT</sub> expression, defined as the ratio of β<sub>IT</sub> and β<sub>C</sub>, was correlated with the respiratory score. <b><i>Results:</i></b> β<sub>IT</sub> expression was found in all 59 recruited newborns with a trend toward higher β<sub>IT</sub> in respiratory ill (score 2, 3) newborns than respiratory healthy newborns ([score 0, 1]; <i>p</i> = 0.066). Seriously ill newborns (score 3) had significantly higher β<sub>IT</sub> than healthy newborns ([score 0], <i>p</i> = 0.010). Healthy preterm infants had significantly higher β<sub>IT</sub> expression than healthy term infants (<i>p</i> = 0.019). <b><i>Conclusions:</i></b> β<sub>IT</sub> is expressed in newborns with higher expression in respiratory ill than respiratory healthy newborns. We hypothesize that β<sub>IT</sub> may have a protective effect in postnatal pulmonary adaptation acting as a physiological inhibitor of β<sub>C</sub> and, therefore, maintaining surfactant in respiratory ill newborns.

scholarly journals Identification through chemical cross-linking of distinct granulocyte- macrophage colony-stimulating factor and interleukin-3 receptors on myeloid leukemic cells, KG-1

Blood ◽  
1989 ◽  
Vol 74 (8) ◽  
pp. 2652-2656 ◽  
Author(s):  
T Gesner ◽  
RA Mufson ◽  
KJ Turner ◽  
SC Clark
Keyword(s):  
Binding Proteins ◽  
Myelogenous Leukemia ◽  
Cross Linking ◽  
Colony Stimulating Factor ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Chemical Cross Linking

Abstract Granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) each bind specifically to a small number of high- affinity receptors present on the surface of the cells of the acute myelogenous leukemia line, KG-1. Through chemical cross-linking of IL-3 and GM-CSF to KG-1 cells, we identified distinct binding proteins for each of these cytokines with approximate molecular masses of 69 and 93 Kd, respectively. Although these two binding proteins are distinct, GM- CSF and IL-3 compete with each other for binding to KG-1 cells. Other cell lines, which express receptors for either factor but not for both do not display this cross-competition for binding with IL-3 and GM-CSF. These findings imply that distinct IL-3 and GM-CSF binding proteins are expressed on the cell surface and that an association exists between these proteins on KG-1 cells.

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