scholarly journals Antifungal Activities of Posaconazole and Granulocyte-Macrophage Colony-Stimulating Factor Ex Vivo and in Mice with Disseminated Infection Due to Scedosporium prolificans

2004 ◽  
Vol 48 (10) ◽  
pp. 3801-3805 ◽  
Author(s):  
M. Simitsopoulou ◽  
C. Gil-Lamaignere ◽  
N. Avramidis ◽  
A. Maloukou ◽  
S. Lekkas ◽  
...  
Keyword(s):  
Ex Vivo ◽  
High Rate ◽  
Invasive Infection ◽  
Colony Stimulating Factor ◽  
Disseminated Infection ◽  
Gm Csf ◽  
Scedosporium Prolificans ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

ABSTRACT Invasive infection due to Scedosporium prolificans is characterized by drug resistance and a high rate of mortality. The effects of posaconazole (POS), an investigational antifungal triazole, murine granulocyte-macrophage colony-stimulating factor (GM-CSF), and their combination against S. prolificans were evaluated ex vivo and in a newly developed murine model of disseminated infection due to this organism. When POS was combined with polymorphonuclear leukocytes from untreated or GM-CSF-treated mice (P < 0.01) ex vivo, it had increased activity in terms of the percentage of hyphal damage. Immunocompetent BALB/c mice were infected with 4 × 104 conidia of S. prolificans via the lateral tail vein. At 24 h postinfection the mice were treated with GM-CSF (5 μg/kg of body weight/day subcutaneously), POS (50 mg/kg/day by gavage), both agents, or saline only. Half of the brain, lung, liver, and kidney from each animal were cultured; and the other half of each organ was processed for histopathology. The mean survival times were 7.0 ± 0.3 days for the controls, 7.4 ± 0.4 days for POS-treated mice, 8.0 ± 0.3 days for GM-CSF-treated mice (P = 0.08 compared with the results for the controls), and 7.3 ± 0.3 days for POS-GM-CSF-treated mice. Fungal burdens (determined as the numbers of CFU per gram of tissue) were found in descending orders of magnitude in the kidneys, brains, livers, and lungs. The burdens were significantly reduced in the brains of GM-CSF-treated mice (P < 0.05) and the livers of POS-treated mice (P < 0.05). The numbers of lesions in the organs closely corresponded to the fungal burdens. GM-CSF tended to prolong survival (P = 0.08 compared with the results for the controls). While the combination of POS and GM-CSF showed enhanced activity ex vivo, it did not increase the activities of the two agents against this highly refractory filamentous fungus in mice.

Granulocyte-Macrophage Colony-Stimulating Factor Upregulates Reduced 5-Lipoxygenase Metabolism in Peripheral Blood Monocytes and Neutrophils in Acquired Immunodeficiency Syndrome

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3897-3905 ◽  
Author(s):  
Michael J. Coffey ◽  
Susan M. Phare ◽  
Sandro Cinti ◽  
Marc Peters-Golden ◽  
Powel H. Kazanjian
Keyword(s):  
Acquired Immunodeficiency Syndrome ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Acquired Immunodeficiency ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Immunodeficiency Syndrome ◽  
Stimulating Factor

Abstract Leukotrienes (LT) are mediators derived from the 5-lipoxygenase (5-LO) pathway, which play a role in host defense, and are synthesized by both monocytes (peripheral blood monocyte [PBM]) and neutrophils (PMN). Because 5-LO metabolism is reduced in alveolar macrophages and PMN from acquired immunodeficiency syndrome (AIDS) subjects, we investigated the synthesis of LT by PBM and PMN from these subjects. There was a reduction (74.2% ± 8.8% of control) in LT synthesis in PBM from human immunodeficiency virus (HIV)-infected compared with normal subjects. Expression of 5-LO (51.2% ± 8.8% of control), and 5-LO activating protein (FLAP) (48.5% ± 8.0% of control) was reduced in parallel. We hypothesized that this reduction in LT synthetic capacity in PBM and PMN was due to reduced cytokine production by CD4 T cells, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). We treated 10 AIDS subjects with GM-CSF for 5 days. PBM 5-LO metabolism ex vivo was selectively increased after GM-CSF therapy and was associated with increased 5-LO and FLAP expression. PMN leukotriene B4(LTB4) synthesis was also augmented and associated with increased 5-LO, FLAP, and cytosolic phospholipase A2 expression. In conclusion, as previously demonstrated for PMN, PBM from AIDS subjects also demonstrate reduced 5-LO metabolism. GM-CSF therapy reversed this defect in both PBM and PMN. In view of the role of LT in antimicrobial function, cytokine administration in AIDS may play a role as adjunct therapy for infections.

scholarly journals Enhancement of the grafting efficiency of transplanted marrow cells by preincubation with interleukin-3 and granulocyte-macrophage colony- stimulating factor

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1599-1606 ◽  
Author(s):  
M Tavassoli ◽  
M Konno ◽  
Y Shiota ◽  
E Omoto ◽  
JJ Minguell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ex Vivo ◽  
Cell Number ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Seeding Efficiency ◽  
Stimulating Factor ◽  
Marrow Cells

Abstract To improve the grafting efficiency of transplanted murine hematopoietic progenitors, we briefly preincubated mouse bone marrow cells with interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) ex vivo before their transplantation into irradiated recipients. This treatment was translated into an increase in the seeding efficiency of colony-forming unit-spleen (CFU-S) and CFU-GM after transplantation. Not only was the concentration of CFU-S in the tibia increased 2 and 24 hours after transplantation, but the total cell number and CFU-S and CFU-GM concentrations were persistently higher in IL-3- and GM-CSF-treated groups 1 to 3 weeks after transplantation. In addition, the survival of animals as a function of transplanted cell number was persistently higher in IL-3- and GM-CSF- treated groups compared with controls. The data indicate that the pretreatment of marrow cells with IL-3 and GM-CSF before transplantation increases the seeding efficiency of hematopoietic stem cells and probably other progenitor cells after transplantation. This increased efficiency may be mediated by upward modulation of homing receptors. Therefore, ex vivo preincubation of donor marrow cells with IL-3 and GM-CSF may be a useful tactic in bone marrow transplantation.

scholarly journals TGF-β combined with M-CSF and IL-4 induces generation of immune inhibitory cord blood dendritic cells capable of enhancing cytokine-induced ex vivo expansion of myeloid progenitors

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2872-2879 ◽  
Author(s):  
Geling Li ◽  
Saeid Abediankenari ◽  
Young-June Kim ◽  
Timothy B. Campbell ◽  
Shigeki Ito ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Cord Blood ◽  
Ex Vivo ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Myeloid Progenitor Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Myeloid Progenitors

Abstract Tolerogenic dendritic cells (DCs) may be valuable in transplantation for silencing immune reaction. Macrophage colony-stimulating factor (M-CSF)/IL-4 induces differentiation of cord blood (CB) monocytes into DCs (M-DCs) with tolerogenic phenotype/function. We assessed whether factors produced by tolerogenic DCs could modulate hematopoiesis. TGF-β1 added to CB M-DC cultures induced bona fide DC morphology (TGF-M-DCs), similar to that of DCs generated with TGF-β and granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-4 (TGF-GM-DCs). Of conditioned media (CM) produced from TGF-M-DCs, TGF-GM-DCs, M-DCs, and GM-DCs, TGF-M-DC CM was the only one that enhanced SCF, Flt3 ligand, and TPO expansion of myeloid progenitor cells ex vivo. This effect was blocked by neutralizing anti–M-CSF Ab, but protein analysis of CM suggested that M-CSF alone was not manifesting enhanced expansion of myeloid progenitors. LPS-stimulated TGF-M-DCs induced T-cell tolerance/anergy as effectively as M-DCs. TGF-M-DCs secreted significantly lower concentrations of progenitor cell inhibitory cytokines and were less potent in activating T cells than TGF-GM-DCs. Functional differences between TGF-M-DCs and TGF-GM-DCs included enhanced responses to LPS-induced ERK, JNK, and P38 activation in TGF-M-DCs and their immune suppressive–skewed cytokine release profiles. TGF-M-DCs appear unique among culture-generated DCs in their capability for silencing immunity while promoting expansion of myeloid progenitors, events that may be of therapeutic value.

scholarly journals Enhancement of the grafting efficiency of transplanted marrow cells by preincubation with interleukin-3 and granulocyte-macrophage colony- stimulating factor

Blood ◽  
1991 ◽  
Vol 77 (7) ◽  
pp. 1599-1606 ◽  
Author(s):  
M Tavassoli ◽  
M Konno ◽  
Y Shiota ◽  
E Omoto ◽  
JJ Minguell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ex Vivo ◽  
Cell Number ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Seeding Efficiency ◽  
Stimulating Factor ◽  
Marrow Cells

To improve the grafting efficiency of transplanted murine hematopoietic progenitors, we briefly preincubated mouse bone marrow cells with interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) ex vivo before their transplantation into irradiated recipients. This treatment was translated into an increase in the seeding efficiency of colony-forming unit-spleen (CFU-S) and CFU-GM after transplantation. Not only was the concentration of CFU-S in the tibia increased 2 and 24 hours after transplantation, but the total cell number and CFU-S and CFU-GM concentrations were persistently higher in IL-3- and GM-CSF-treated groups 1 to 3 weeks after transplantation. In addition, the survival of animals as a function of transplanted cell number was persistently higher in IL-3- and GM-CSF- treated groups compared with controls. The data indicate that the pretreatment of marrow cells with IL-3 and GM-CSF before transplantation increases the seeding efficiency of hematopoietic stem cells and probably other progenitor cells after transplantation. This increased efficiency may be mediated by upward modulation of homing receptors. Therefore, ex vivo preincubation of donor marrow cells with IL-3 and GM-CSF may be a useful tactic in bone marrow transplantation.

scholarly journals The Effects of Ex Vivo Administration of Granulocyte-Macrophage Colony-Stimulating Factor and Endotoxin on Cytokine Release of Whole Blood Are Determined by Priming Conditions

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
A. Nierhaus ◽  
J. Linssen ◽  
M. S. Winkler ◽  
D. P. Frings ◽  
S. Kluge
Keyword(s):  
Ex Vivo ◽  
Endotoxin Tolerance ◽  
Colony Stimulating Factor ◽  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Healthy Donors ◽  
Factor Alpha ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Background. Lipopolysaccharide- (LPS-) induced tumour necrosis factor alpha (TNFα) secretion in critically ill patients can be considered as a measure of immune responsiveness. It can be enhanced by granulocyte-macrophage colony stimulating factor (GM-CSF). We investigated the effect of GM-CSF on ex vivo stimulated cytokine production using various preincubation regimens in healthy donors and patients with sepsis.Results. The maxima for the stimuli occurred 3 hours after stimulation. In donors, there was an increase(p<0.001)of LPS-induced TNFαlevels following incubation with GM-CSF. Thesimultaneousincubation with GM-CSF and LPS caused an inhibition of TNFαproduction(p<0.001).Postincubationwith GM-CSF did not yield any difference. In patients, preincubation with GM-CSF yielded an enhanced ex vivo TNFα-response when TNFαlevels were low. Patients with increased TNFαconcentrations did not show a GM-CSF stimulation effect. The GM-CSF preincubation yielded an increase of IL-8 production in patients and donors.Conclusions. This study demonstrates the immune-modulating properties of GM-CSF depending on the absence or presence of LPS or systemic TNFα. The timing of GM-CSF administration may be relevant for the modulation of the immune system in sepsis. The lack of stimulation in patients with high TNFαmay represent endotoxin tolerance.

Granulocyte-Macrophage Colony-Stimulating Factor Upregulates Reduced 5-Lipoxygenase Metabolism in Peripheral Blood Monocytes and Neutrophils in Acquired Immunodeficiency Syndrome

Blood ◽  
1999 ◽  
Vol 94 (11) ◽  
pp. 3897-3905 ◽  
Author(s):  
Michael J. Coffey ◽  
Susan M. Phare ◽  
Sandro Cinti ◽  
Marc Peters-Golden ◽  
Powel H. Kazanjian
Keyword(s):  
Acquired Immunodeficiency Syndrome ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Acquired Immunodeficiency ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Immunodeficiency Syndrome ◽  
Stimulating Factor

Leukotrienes (LT) are mediators derived from the 5-lipoxygenase (5-LO) pathway, which play a role in host defense, and are synthesized by both monocytes (peripheral blood monocyte [PBM]) and neutrophils (PMN). Because 5-LO metabolism is reduced in alveolar macrophages and PMN from acquired immunodeficiency syndrome (AIDS) subjects, we investigated the synthesis of LT by PBM and PMN from these subjects. There was a reduction (74.2% ± 8.8% of control) in LT synthesis in PBM from human immunodeficiency virus (HIV)-infected compared with normal subjects. Expression of 5-LO (51.2% ± 8.8% of control), and 5-LO activating protein (FLAP) (48.5% ± 8.0% of control) was reduced in parallel. We hypothesized that this reduction in LT synthetic capacity in PBM and PMN was due to reduced cytokine production by CD4 T cells, such as granulocyte-macrophage colony-stimulating factor (GM-CSF). We treated 10 AIDS subjects with GM-CSF for 5 days. PBM 5-LO metabolism ex vivo was selectively increased after GM-CSF therapy and was associated with increased 5-LO and FLAP expression. PMN leukotriene B4(LTB4) synthesis was also augmented and associated with increased 5-LO, FLAP, and cytosolic phospholipase A2 expression. In conclusion, as previously demonstrated for PMN, PBM from AIDS subjects also demonstrate reduced 5-LO metabolism. GM-CSF therapy reversed this defect in both PBM and PMN. In view of the role of LT in antimicrobial function, cytokine administration in AIDS may play a role as adjunct therapy for infections.

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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