scholarly journals Epstein-Barr Virus-Encoded BARF1 Protein is a Decoy Receptor for Macrophage Colony Stimulating Factor and Interferes with Macrophage Differentiation and Activation

2012 ◽  
Vol 25 (6) ◽  
pp. 461-470 ◽  
Author(s):  
Eveline K. Hoebe ◽  
Tessa Y.S. Le Large ◽  
Nicolas Tarbouriech ◽  
Dinja Oosterhoff ◽  
Tanja D. De Gruijl ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Colony Stimulating Factor ◽  
Macrophage Differentiation ◽  
Decoy Receptor ◽  
Barr Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Epstein Barr ◽  
Macrophage Colony ◽  
Stimulating Factor

Antibodies Binding Granulocyte–Macrophage Colony Stimulating Factor Produced by Cord Blood-Derived B Cell Lines Immortalized by Epstein–Barr Virus in Vitro

2000 ◽  
Vol 204 (2) ◽  
pp. 114-127 ◽  
Author(s):  
Roberto P. Revoltella ◽  
Leopoldo Laricchia Robbio ◽  
Anna Marina Liberati ◽  
Gigliola Reato ◽  
Robin Foa ◽  
...  
Keyword(s):  
Cord Blood ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Colony Stimulating Factor ◽  
Barr Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Epstein Barr ◽  
Macrophage Colony ◽  
Stimulating Factor

Epstein-Barr virus inhibits the development of dendritic cells by promoting apoptosis of their monocyte precursors in the presence of granulocyte macrophage–colony-stimulating factor and interleukin-4

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3725-3734 ◽  
Author(s):  
LiQi Li ◽  
Daorong Liu ◽  
Lindsey Hutt-Fletcher ◽  
Andrew Morgan ◽  
Maria G. Masucci ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Epstein Barr Virus ◽  
Interleukin 4 ◽  
Viral Gene ◽  
Colony Stimulating Factor ◽  
Barr Virus ◽  
Macrophage Colony Stimulating Factor ◽  
Epstein Barr ◽  
Macrophage Colony ◽  
Stimulating Factor

Epstein-Barr virus (EBV) is a tumorigenic human herpesvirus that persists for life in healthy immunocompetent carriers. The viral strategies that prevent its clearance and allow reactivation in the face of persistent immunity are not well understood. Here we demonstrate that EBV infection of monocytes inhibits their development into dendritic cells (DCs), leading to an abnormal cellular response to granulocyte macrophage–colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) and to apoptotic death. This proapoptotic activity was not affected by UV inactivation and was neutralized by EBV antibody-positive human sera, indicating that binding of the virus to monocytes is sufficient to alter their response to the cytokines. Experiments with the relevant blocking antibodies or with mutated EBV strains lacking either the EBV envelope glycoprotein gp42 or gp85 demonstrated that interaction of the trimolecular gp25–gp42–gp85 complex with the monocyte membrane is required for the effect. Our data provide the first evidence that EBV can prevent the development of DCs through a mechanism that appears to bypass the requirement for viral gene expression, and they suggest a new strategy for interference with the function of DCs during the initiation and maintenance of virus-specific immune responses.

scholarly journals The Role of TGFβ1 and Macrophage Differentiation in MSU Crystal-Induced Inflammation

2021 ◽  
Author(s):  
◽  
Stefanie Steiger
Keyword(s):  
Bone Marrow ◽  
Inflammatory Response ◽  
Surface Marker ◽  
Acute Gout ◽  
Colony Stimulating Factor ◽  
Macrophage Differentiation ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Msu Crystals

<p>Gout is a painful form of inflammatory arthritis that is caused by the deposition of monosodium urate (MSU) crystals in the joints. MSU crystals trigger a local inflammatory response initiated by resident macrophages followed by a large infiltration of leukocytes. The spontaneous resolution of acute gout is associated with the production of transforming growth factor β1 (TGFβ1). The overall objectives of this thesis were to investigate mechanisms that lead to TGFβ1 production and contribute to the resolution of acute gout, the effect of TGFβ1 on the functional phenotype of differentiated macrophages, and possible changes in surface marker expression by macrophages in response to MSU crystals.  To determine macrophage-independent sources of TGFβ1 during the resolution of acute gout and how TGFβ1 production altered MSU crystal-recruited neutrophil functions, neutrophils were purified from MSU crystal-treated mice when levels of TGFβ1 were high. MSU crystal-recruited neutrophils and circulating blood neutrophils were identified as TGFβ1⁺ cells. The mechanism for TGFβ1 production by neutrophils was associated with their ability to phagocytose apoptotic neutrophils. TGFβ1 produced by canibalising neutrophils inhibited both respiratory burst and interleukin-1β (IL-1β) production by MSU crystal-activated neutrophils ex vivo. Importantly, neutrophils from MSU crystal-challenged mice treated with TGFβ1 neutralising antibody in vivo produced elevated levels of superoxide but neutrophil IL-1β production was unaffected. These results show that TGFβ1 produced by canibalising neutrophils can actively suppress neutrophil inflammatory functions and therefore make a significant contribution towards the resolution of gouty inflammation.  To investigate the effect of TGFβ1 on macrophage differentiation in vitro, granulocyte macrophage colony-stimulating factor (GM-CSF) bone marrow macrophages (GM-BMMs) and macrophage colony-stimulating factor (M-CSF) bone marrow macrophages (M-BMMs) were generated in the presence of TGFβ1. TGFβ1 was found to drive a hyper-inflammatory GM-BMM phenotype, while contributing to the differentiation of a hypo-inflammatory M-BMM phenotype specifically in response to MSU crystals. Increased IL-1β production by TGFβ1-differentiated GM-BMMs was associated with enhanced NOD like receptor family, pyrin domain-containing 3 (NLRP3) in ammasome activation and caspase 1/caspase 8 interaction, and a down-regulation of receptor-interacting serine/threonine-protein kinase 3 (RIP3) triggered by MSU crystals. At the same, TGFβ1 inhibited antigen-specific T cell proliferation by GM-BMMs. In contrast, TGFβ1-treated M-BMMs down-regulated the expression of active IL-1β that correlated with decreased IL-1β production, and upregulated RIP3 expression in response to MSU crystals. These data indicate that TGFβ1-treated GM-BMMs exhibited a hyper-inflammatory response to MSU crystal stimulation, whereas M-BMMs were found to be hypo-responsive.  Macrophages were found to upregulate the surface marker NK1.1, which is primarily expressed on natural killer (NK) cells, and occured as a consequence of phagocytosis. Following phagocytosis of MSU crystals, activated macrophages produced IL-1β and tumour necrosis factor ⍺ (TNF⍺), which triggered the upregulation of NK1.1 expression. Macrophage NK1.1 expression is an activation-driven event specifc to MSU crystals. However, phagocytosis of apoptotic neutrophils also triggered the upregulation of NK1.1 by macrophages, a non-inflammatory event that is characteristic for the resolution of acute inflammation. These findings suggest that macrophages may develop NK cell-like properties initiated by an activation-driven or apoptotic cell clearance mechanism.  Taken together, the results of this thesis indicate that canibalising neutrophils self-regulate their inflammatory functions via TGFβ1 and that TGFβ1 drives a hyper-inflammatory GM-BMM phenotype, while shutting down inflammatory functions of M-BMMs. These data highlight a regulatory role for TGFβ1 during acute gouty inflammation.</p>

scholarly journals Synergistic effect of granulocyte-macrophage colony-stimulating factor and 1,25-dihydroxyvitamin D3 on the differentiation of the human monocytic cell line U937

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 619-624
Author(s):  
SH Zuckerman ◽  
YM Surprenant ◽  
J Tang
Keyword(s):  
Synergistic Effect ◽  
Antigen Expression ◽  
Peripheral Blood Monocyte ◽  
Colony Stimulating Factor ◽  
Macrophage Differentiation ◽  
Dihydroxyvitamin D3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The human monoblastlike cell line U937 can be induced to differentiate by a variety of agents including gamma-interferon, phorbol esters, retinoic acid, and 1,25-dihydroxyvitamin D3 (VD3). Incubation of U937 with 1 to 1,000 units of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) did not induce macrophage differentiation. A synergistic effect on macrophage differentiation was observed, however, when U937 was cocultured with 10(-8) mol/L VD3 plus 50 U/mL GM-CSF. GM-CSF-plus VD3-treated cells demonstrated significant increases in OKM1 antigen expression, increased chemokinesis and chemotaxis, and increased Fc receptor-mediated erythrophagocytosis. Human peripheral blood monocyte cultures also demonstrated increased OKM1 antigen expression and chemotaxis when incubated with 50 to 500 U/mL of GM-CSF for 48 to 72 hours. VD3, however, was not necessary for the increases in effector function observed for GM-CSF-stimulated monocyte cultures. In distinction to the synergistic effect of GM-CSF on VD3-induced differentiation of U937, recombinant human granulocyte colony-stimulating factor (G-CSF) at comparable concentrations had no augmenting effect over that observed for VD3 alone. These results suggest that GM-CSF, in the presence of other physiological stimuli, can induce significant phenotypic changes in GM-CSF-nonresponsive cells of the monocytic lineage and can increase the effector functions of GM- CSF-responsive peripheral blood monocyte cultures.

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