scholarly journals Antibody to Granulocyte-Macrophage Colony-Stimulating Factor Is a Dominant Anti-Cytokine Activity in Human IgG Preparations

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2054-2061 ◽  
Author(s):  
Morten Svenson ◽  
Morten Bagge Hansen ◽  
Christian Ross ◽  
Marcus Diamant ◽  
Klaus Rieneck ◽  
...  
Keyword(s):  
Pharmaceutical Preparations ◽  
Polymorphonuclear Cells ◽  
High Avidity ◽  
Colony Stimulating Factor ◽  
Human Igg ◽  
Gm Csf ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Pharmaceutical preparations of normal human immunoglobulin (IgG) are known to contain high-avidity and neutralizing antibodies (Ab) to the cytokines interleukin (IL)-1α, IL-6, and interferon (IFN)α. To test for other cytokine Ab, 23 batches of IgG were tested for saturable binding to eight 125I-labeled recombinant cytokines. All batches bound granulocyte-macrophage colony-stimulating factor (GM-CSF) with high avidity (Kav ≈ 10 pmol/L) and capacities of up to 5 μmol GM-CSF/mol IgG. Only 1 of 15 batches bound IL-5, also with high avidity, whereas 13 of 15 batches bound to IL-10 but with lower capacities and avidities. None of the IgG preparations bound IL-1 receptor antagonist (IL-1ra), IL-2, IL-3, IL-4, or G-CSF. Cross-binding and absorption analyses revealed identical or slightly stronger binding of recombinant GM-CSF, IL-5, and IL-10 than their native counterparts. GM-CSF–IgG complexes did not bind to cellular GM-CSF receptors, but Fc-dependent binding occurred to blood polymorphonuclear cells. Increased binding of GM-CSF to patient sera correlated positively with the binding capacities of infused IgG preparations. Patient and normal sera did not interfere with the binding of Ab to GM-CSF. From these and previous experiments, we conclude that pools of normal human IgG contain variable amounts of specific and high-avidity Ab to some cytokines, and that Ab to GM-CSF constitute a dominant anti-cytokine activity in these preparations. These Ab are available for reactionin vivo following IgG therapy.

scholarly journals Antibody to Granulocyte-Macrophage Colony-Stimulating Factor Is a Dominant Anti-Cytokine Activity in Human IgG Preparations

Blood ◽  
1998 ◽  
Vol 91 (6) ◽  
pp. 2054-2061 ◽  
Author(s):  
Morten Svenson ◽  
Morten Bagge Hansen ◽  
Christian Ross ◽  
Marcus Diamant ◽  
Klaus Rieneck ◽  
...  
Keyword(s):  
Pharmaceutical Preparations ◽  
Polymorphonuclear Cells ◽  
High Avidity ◽  
Colony Stimulating Factor ◽  
Human Igg ◽  
Gm Csf ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Pharmaceutical preparations of normal human immunoglobulin (IgG) are known to contain high-avidity and neutralizing antibodies (Ab) to the cytokines interleukin (IL)-1α, IL-6, and interferon (IFN)α. To test for other cytokine Ab, 23 batches of IgG were tested for saturable binding to eight 125I-labeled recombinant cytokines. All batches bound granulocyte-macrophage colony-stimulating factor (GM-CSF) with high avidity (Kav ≈ 10 pmol/L) and capacities of up to 5 μmol GM-CSF/mol IgG. Only 1 of 15 batches bound IL-5, also with high avidity, whereas 13 of 15 batches bound to IL-10 but with lower capacities and avidities. None of the IgG preparations bound IL-1 receptor antagonist (IL-1ra), IL-2, IL-3, IL-4, or G-CSF. Cross-binding and absorption analyses revealed identical or slightly stronger binding of recombinant GM-CSF, IL-5, and IL-10 than their native counterparts. GM-CSF–IgG complexes did not bind to cellular GM-CSF receptors, but Fc-dependent binding occurred to blood polymorphonuclear cells. Increased binding of GM-CSF to patient sera correlated positively with the binding capacities of infused IgG preparations. Patient and normal sera did not interfere with the binding of Ab to GM-CSF. From these and previous experiments, we conclude that pools of normal human IgG contain variable amounts of specific and high-avidity Ab to some cytokines, and that Ab to GM-CSF constitute a dominant anti-cytokine activity in these preparations. These Ab are available for reactionin vivo following IgG therapy.

scholarly journals Secretion of cytokines (interleukins-1 alpha, -3, and -6 and granulocyte-macrophage colony-stimulating factor) by normal human bone marrow megakaryocytes

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 685-691 ◽  
Author(s):  
C Wickenhauser ◽  
J Lorenzen ◽  
J Thiele ◽  
A Hillienhof ◽  
K Jungheim ◽  
...  
Keyword(s):  
Plaque Assay ◽  
Secretory Activity ◽  
Colony Stimulating Factor ◽  
Rt Pcr ◽  
Gm Csf ◽  
Clear Cut ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The effects of cytokine stimulation [recombinant human interleukin (rhIL)-1 alpha, rhIL-3, rhIL-6, rhIL-11, and rh granulocyte-macrophage colony-stimulating factor (GM-CSF)] on the secretory activity of normal human megakaryocytes were studied by means of the reverse hemolytic plaque assay (RHPA) in enriched cell preparations. This test facilitates an extremely sensitive determination of cytokine secretion at the single-cell level, together with the clear-cut identification of each immunostained (CD61) secretory active megakaryocyte. Moreover, the reverse transcriptase-polymerase chain reaction (RT-PCR) was used to investigate the expression of IL-6, IL-6 receptor (IL-6R), IL-9, IL-10, IL-12, and IL-13 mRNA in highly concentrated megakaryocyte preparations. In comparison with the spontaneous secretion rate, stimulation with rhIL-1 alpha, rhIL-6, and rhGM-CSF failed to induce a significant increase in the release of cytokines by CD61+ cells. On the other hand, both rhIL-3 and, in a less pronounced way, rhIL-11 exerted a marked effect on IL-6 secretion. Additionally, after stimulation with rhIL-3, a significant enhancement of the secretion of IL-3 and GM-CSF, but not of IL-1 alpha, could be observed. Using the RT-PCR, a significant induction of IL-6 expression could be appreciated in the enriched megakaryocyte population (60% to 80%) stimulated with rhIL-3. The results of this study provide persuasive evidence that a number of cytokines are synthesized and secreted by human megakaryocytes and not only by hematopoietic stroma cells. These data suggest the existence of autocrine and paracrine mechanisms that may influence maturation and differentiation of megakaryocytes as well as act on various stroma cells to sustain an appropriate hematopoietic micro-environment.

scholarly journals Proliferation of normal human promyelocytes and myelocytes after a single pulse stimulation by purified GM-CSF or G-CSF

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 640-645
Author(s):  
CG Begley ◽  
NA Nicola ◽  
D Metcalf
Keyword(s):  
Single Pulse ◽  
Colony Stimulating Factor ◽  
Single Exposure ◽  
Gm Csf ◽  
Blast Cells ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Pulse Stimulation

Enriched populations of either normal human promyelocytes and myelocytes or blast cells were obtained by fluorescence-activated cell sorting with the monoclonal antibody WEM-G11. These populations were used to study the effect of pulse stimulation by purified recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) or cross-reacting purified murine granulocyte colony-stimulating factor (G- CSF). Maximal clone formation by promyelocytes and myelocytes was observed in 1-mL agar cultures stimulated continuously with 400 units of either CSF and in cultures of cells that were pulse stimulated by 3,200 units (or greater) of either CSF. Pulse stimulation by 800 units of GM-CSF or G-CSF generated 75% clone formation, and pulse stimulation by 200 units CSF gave 50% clone formation. The majority of clones formed by pulse-stimulated cells were only two cells in size; however, some clones were up to 15 cells in size after a single exposure to CSF. Clone formation was not observed in cultures of blast cell populations after a single pulse stimulation with GM-CSF or G-CSF.

scholarly journals Human granulocyte-macrophage progenitors and their sensitivity to cytotoxins: analysis by limiting dilution

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1773-1776
Author(s):  
KE Barber ◽  
PS Crosier ◽  
S Gillis ◽  
JD Watson
Keyword(s):  
Progenitor Cells ◽  
Human Growth ◽  
Differential Sensitivity ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Limiting Dilution

Limiting dilution analysis of granulocyte-macrophage progenitor cells was performed by using adherent and T cell-depleted normal human bone marrow and the recombinant human growth factors, granulocyte colony- stimulating factor (G-CSF) and granulocyte-macrophage colony- stimulating factor (GM-CSF). Estimated frequencies for progenitor cells responding to G-CSF were one in 489 for colonies scored at day 7, and one in 1,015 for day 14 colonies. For GM-CSF the frequencies were one in 1,407 (day 7) and one in 574 (day 14). The effects of tumor necrosis factor (TNF) and lymphotoxin (LT) on the frequency of progenitors responding to either G-CSF or GM-CSF was determined. Both TNF and LT inhibited the response of cells to G-CSF, and in these cultures the frequency of progenitor cells that responded to G-CSF was reduced to less than one in 100,000 cells. In contrast, the frequency of cells able to form colonies in cultures stimulated with GM-CSF was unaltered by either cytotoxin. This differential sensitivity to cytotoxins suggests that either G-CSF and GM-CSF are acting on separate granulocyte progenitor populations or that TNF and LT selectively influence the biochemical pathways associated with the activation of receptors for G-CSF.

scholarly journals Human granulocyte-macrophage progenitors and their sensitivity to cytotoxins: analysis by limiting dilution

Blood ◽  
1987 ◽  
Vol 70 (6) ◽  
pp. 1773-1776 ◽  
Author(s):  
KE Barber ◽  
PS Crosier ◽  
S Gillis ◽  
JD Watson
Keyword(s):  
Progenitor Cells ◽  
Human Growth ◽  
Differential Sensitivity ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Limiting Dilution

Abstract Limiting dilution analysis of granulocyte-macrophage progenitor cells was performed by using adherent and T cell-depleted normal human bone marrow and the recombinant human growth factors, granulocyte colony- stimulating factor (G-CSF) and granulocyte-macrophage colony- stimulating factor (GM-CSF). Estimated frequencies for progenitor cells responding to G-CSF were one in 489 for colonies scored at day 7, and one in 1,015 for day 14 colonies. For GM-CSF the frequencies were one in 1,407 (day 7) and one in 574 (day 14). The effects of tumor necrosis factor (TNF) and lymphotoxin (LT) on the frequency of progenitors responding to either G-CSF or GM-CSF was determined. Both TNF and LT inhibited the response of cells to G-CSF, and in these cultures the frequency of progenitor cells that responded to G-CSF was reduced to less than one in 100,000 cells. In contrast, the frequency of cells able to form colonies in cultures stimulated with GM-CSF was unaltered by either cytotoxin. This differential sensitivity to cytotoxins suggests that either G-CSF and GM-CSF are acting on separate granulocyte progenitor populations or that TNF and LT selectively influence the biochemical pathways associated with the activation of receptors for G-CSF.

scholarly journals Proliferation of normal human promyelocytes and myelocytes after a single pulse stimulation by purified GM-CSF or G-CSF

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 640-645 ◽  
Author(s):  
CG Begley ◽  
NA Nicola ◽  
D Metcalf
Keyword(s):  
Single Pulse ◽  
Colony Stimulating Factor ◽  
Single Exposure ◽  
Gm Csf ◽  
Blast Cells ◽  
Normal Human ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Pulse Stimulation

Abstract Enriched populations of either normal human promyelocytes and myelocytes or blast cells were obtained by fluorescence-activated cell sorting with the monoclonal antibody WEM-G11. These populations were used to study the effect of pulse stimulation by purified recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) or cross-reacting purified murine granulocyte colony-stimulating factor (G- CSF). Maximal clone formation by promyelocytes and myelocytes was observed in 1-mL agar cultures stimulated continuously with 400 units of either CSF and in cultures of cells that were pulse stimulated by 3,200 units (or greater) of either CSF. Pulse stimulation by 800 units of GM-CSF or G-CSF generated 75% clone formation, and pulse stimulation by 200 units CSF gave 50% clone formation. The majority of clones formed by pulse-stimulated cells were only two cells in size; however, some clones were up to 15 cells in size after a single exposure to CSF. Clone formation was not observed in cultures of blast cell populations after a single pulse stimulation with GM-CSF or G-CSF.

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.

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