scholarly journals The diadenosine polyphosphates Ap3A and Ap4A and adenosine triphosphate interact with granulocyte-macrophage colony-stimulating factor to delay neutrophil apoptosis: implications for neutrophil: platelet interactions during inflammation

Blood ◽  
1996 ◽  
Vol 87 (8) ◽  
pp. 3442-3449 ◽  
Author(s):  
L Gasmi ◽  
AG McLennan ◽  
SW Edwards
Keyword(s):  
Adenosine Triphosphate ◽  
Immune Cell ◽  
Cellular Morphology ◽  
Neutrophil Apoptosis ◽  
Colony Stimulating Factor ◽  
Diadenosine Polyphosphates ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Incubation of neutrophils with cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF) delays their loss of function and changes in cellular morphology that are characteristic of apoptosis. Adenosine triphosphate (ATP) and the diadenosine polyphosphates Ap4A and AP3A were almost as effective as GM-CSF in delaying neutrophil apoptosis. The nucleotides could thus preserve cellular morphology, protect against chromatin fragmentation, and preserve functions such as NADPH oxidase activity and expression of CD16. Moreover, addition of ATP, AP3A and AP4A together with GM-CSF resulted in more pronounced protection from apoptosis than was observed during incubation with either the cytokine or the nucleotides alone. Because ATP, Ap3A, and AP4A may be secreted from activated platelets, these observations suggest that platelet-derived products, perhaps acting in combination with endothelial-derived or immune cell-derived cytokines, can regulate neutrophil function during certain types of inflammation.

scholarly journals Granulocyte Macrophage Colony-Stimulating Factor

2001 ◽  
Vol 194 (7) ◽  
pp. 873-882 ◽  
Author(s):  
Jonathan L. McQualter ◽  
Rima Darwiche ◽  
Christine Ewing ◽  
Manabu Onuki ◽  
Thomas W. Kay ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Cell ◽  
Specific Antigen ◽  
Demyelinating Diseases ◽  
Colony Stimulating Factor ◽  
Cns Inflammation ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, can be induced by immunization with a number of myelin antigens. In particular, myelin oligodendrocyte glycoprotein, a central nervous system (CNS)-specific antigen expressed on the myelin surface, is able to induce a paralytic MS-like disease with extensive CNS inflammation and demyelination in several strains of animals. Although not well understood, the egress of immune cells into the CNS in EAE is governed by a complex interplay between pro and antiinflammatory cytokines and chemokines. The hematopoietic growth factor, granulocyte macrophage colony-stimulating factor (GM-CSF), is considered to play a central role in maintaining chronic inflammation. The present study was designed to investigate the previously unexplored role of GM-CSF in autoimmune-mediated demyelination. GM-CSF−/− mice are resistant to EAE, display decreased antigen-specific proliferation of splenocytes, and fail to sustain immune cell infiltrates in the CNS, thus revealing key activities for GM-CSF in the development of inflammatory demyelinating lesions and control of migration and/or proliferation of leukocytes within the CNS. These results hold implications for the pathogenesis of inflammatory and demyelinating diseases and may provide the basis for more effective therapies for inflammatory diseases, and more specifically for multiple sclerosis.

Granulocyte macrophage colony-stimulating factor and the intestinal innate immune cell homeostasis in Crohn's disease

2014 ◽  
Vol 306 (6) ◽  
pp. G455-G465 ◽  
Author(s):  
Jan Däbritz
Keyword(s):  
Crohn’S Disease ◽  
Immune Cell ◽  
Innate Immune ◽  
Innate Immune Cell ◽  
Colony Stimulating Factor ◽  
Cell Homeostasis ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Current literature consolidates the view of Crohn's disease (CD) as a form of immunodeficiency highlighting dysregulation of intestinal innate immunity in the pathogenesis of CD. Intestinal macrophages derived from blood monocytes play a key role in sustaining the innate immune homeostasis in the intestine, suggesting that the monocyte/macrophage compartment might be an attractive therapeutic target for the management of CD. Granulocyte macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that also promotes myeloid cell activation, proliferation, and differentiation. GM-CSF has a protective effect in human CD and mouse models of colitis. However, the role of GM-CSF in immune and inflammatory reactions in the intestine is not well defined. Beneficial effects exerted by GM-CSF during intestinal inflammation could relate to modulation of the mucosal barrier function in the intestine, including epithelial cell proliferation, survival, restitution, and immunomodulatory actions. The aim of this review is to summarize potential mechanistic roles of GM-CSF in intestinal innate immune cell homeostasis and to highlight its central role in maintenance of the intestinal immune barrier in the context of immunodeficiency in CD.

scholarly journals Toxoplasma gondii Induces Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Secretion by Human Fibroblasts: Implications for Neutrophil Apoptosis

2002 ◽  
Vol 70 (11) ◽  
pp. 6048-6057 ◽  
Author(s):  
Jacqueline Y. Channon ◽  
Kristin A. Miselis ◽  
Laurie A. Minns ◽  
Chaitali Dutta ◽  
Lloyd H. Kasper
Keyword(s):  
Conditioned Medium ◽  
Human Fibroblasts ◽  
Neutrophil Apoptosis ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Soluble Mediator ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

ABSTRACT Human neutrophils are rescued from apoptosis following incubation with once-washed, fibroblast-derived Toxoplasma gondii tachyzoites. Both infected and uninfected neutrophils are rescued, implicating a soluble mediator. In this study we investigated the origin and identity of this soluble mediator. Neutrophils were incubated either with purified tachyzoites or with conditioned medium derived from T. gondii-infected human fibroblasts. Conditioned medium was found to be a potent stimulus that delayed neutrophil apoptosis up to 72 h, whereas purified and extensively washed tachyzoites had no effect. Delayed apoptosis correlated with up-regulation of the neutrophil antiapoptotic protein, Mcl-1, and the neutrophil interleukin 3 receptor α subunit (IL-3Rα), suggesting a role for granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF and granulocyte colony-stimulating factor (G-CSF) were measurable in conditioned medium by enzyme-linked immunosorbent assay. Neutralizing antibodies to GM-CSF and G-CSF were additive in abrogating delayed neutrophil apoptosis induced by conditioned medium. Inhibitors of Src family tyrosine kinases, Gi proteins, phosphatidylinositol 3-kinase, p44 erk1 and p42 erk2 mitogen-activated protein kinases, and Jak2 kinases partially attenuated the effect of conditioned medium, consistent with a role for G-CSF and/or GM-CSF. Hence, delayed neutrophil apoptosis is mediated by GM-CSF and G-CSF secreted by T. gondii-infected human fibroblasts. This enhanced neutrophil survival may contribute to the robust proinflammatory response elicited in the T. gondii-infected host.

scholarly journals Effects of granulocyte-macrophage colony-stimulating factor and cyclic AMP interaction on human neutrophil apoptosis

1998 ◽  
Vol 7 (6) ◽  
pp. 391-396 ◽  
Author(s):  
Cosimo Tortorella ◽  
Giuseppina Piazzolla ◽  
Felice Spaccavento ◽  
Salvatore Antonaci
Keyword(s):  
Cyclic Amp ◽  
Camp Signaling ◽  
Neutrophil Apoptosis ◽  
Colony Stimulating Factor ◽  
Dibutyryl Camp ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Neutrophil Survival ◽  
Stimulating Factor

The current study was undertaken to evaluate the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and cyclic AMP (cAMP) signaling interaction on human neutrophil apoptosis, either occurring spontaneously or induced by Fas antigen activation. Results show that GM-CSF, dibutyryl cAMP (a cAMP analog) and forskolin (an adenylate cyclase activator) are all able to suppress spontaneous neutrophil cell death. Of note however, when GM-CSF is used in combination with cAMP-elevating agents, an additive effect on neutrophil survival is observed with dibutyryl cAMP only, whereas supplementation of cell cultures with GM-CSF and forskolin results in a progressive reduction of antiapoptotic effects exerted by the single compounds. Moreover, although dibutyryl cAMP and forskolin do not affect Fas-triggered apoptotic events, they are still able to modulate the GM-CSF capacity to prolong neutrophil survival following anti-Fas IgM cell challenge, with effects similar to those respectively exerted on spontaneous neutrophil apoptosis. The data indicate that GM-CSF m ay negatively modulate the cAMP-mediated antiapoptotic pathway in human neutrophils, likely via the inhibition of adenylate cyclase activity. This would prevent an abnormal neutrophil survival as a result of cAMP signaling stimulation, which provides a novel insight into the role of GM-CSF as a physiological regulator of myeloid cell turnover.

scholarly journals Application of Western Blot for detection of neutrophil apoptosis-related proteins

2009 ◽  
Vol 57 (1) ◽  
pp. 97-104
Author(s):  
Petr Sláma
Keyword(s):  
Western Blot ◽  
Myeloid Cell ◽  
Neutrophil Apoptosis ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Western Blot Method ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Related Proteins ◽  
Stimulating Factor

The aim of this study was to evaluate suitability of using Western Blot for detection of neutrophil apo­pto­sis and neutrophil apoptosis-related proteins, respectively. Neutrophils were isolated from blood of healthy adult donors and incubated with G-CSF (granulocyte colony stimulating factor), GM-CSF (granulocyte-macrophage colony stimulating factor), ATP (adenosine triphosphate) and FMLP (N-formyl-methionyl-leucyl-phenylalanine). The neutrophils were incubated 4, 8 and 20 hours at 37 °C. In this assay, an expression of Mcl-1 (myeloid cell leukemia 1), XIAP (X-linked inhibitor of apoptosis) and gelsolin was analysed by Western Blot method. The results showed that Western Blot is a suitable method for detection of neutrophil apoptosis-related proteins and detection of neutrophil apoptosis, respectively.

The dual effects of TNFα on neutrophil apoptosis are mediated via differential effects on expression of Mcl-1 and Bfl-1

Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 878-884 ◽  
Author(s):  
Andrew Cross ◽  
Robert J. Moots ◽  
Steven W. Edwards
Keyword(s):  
Inflammatory Diseases ◽  
Neutrophil Apoptosis ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Low Concentrations ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Opposing Effects ◽  
Neutrophil Survival ◽  
Stimulating Factor

Neutrophils have a very short half-life in the circulation, undergoing rapid death by apoptosis, but a number of agents can either delay or accelerate the rate at which these cells undergo death. TNFα can exert opposing, concentration-dependent effects on neutrophils to either accelerate their apoptosis or enhance their survival. We show that TNFα greatly increases the rate of turnover of Mcl-1, an antiapoptotic protein that plays a key role in neutrophil survival. In contrast to Mcl-1 turnover in control- or granulocyte-macrophage colony-stimulating factor (GM-CSF)–treated neutrophils that occurs via the proteasome, TNFα-accelerated Mcl-1 turnover occurs via activation of caspases. Mcl-1–depleted cells thus have accelerated rates of apoptosis. While TNFα had no effect on MCL-1 transcription, it induced expression of another antiapoptotic molecule, BFL-1. Low concentrations of TNFα (≤ 1 ng/mL) stimulated BFL-1 expression, whereas higher concentrations (≥ 10 ng/mL) triggered caspase-dependent acceleration of Mcl-1 turnover. These opposing effects on 2 separate antiapoptotic systems of neutrophils explain the divergent effects of TNFα on neutrophil apoptosis and have important implications for understanding how TNFα may affect immune function in inflammatory diseases.

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.

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