scholarly journals Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous CSF-1 Activation

2021 ◽  
Vol 22 (7) ◽  
pp. 3532
Author(s):  
Yu-Chih Chen ◽  
Yin-Siew Lai ◽  
Yan-Der Hsuuw ◽  
Ko-Tung Chang
Keyword(s):  
Single Agent ◽  
Interleukin 4 ◽  
Phosphatidylinositol 3 Kinase ◽  
Long Run ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Necrosis Factor ◽  
Enhance Tumor Growth ◽  
Alternatively Activated

Macrophage colony-stimulating factor (M-CSF or CSF-1) is known to have a broad range of actions on myeloid cells maturation, including the regulation of macrophage differentiation, proliferation and survival. Macrophages generated by M-CSF stimulus have been proposed to be alternatively activated or M2 phenotype. M-CSF is commonly overexpressed by tumors and is also known to enhance tumor growth and aggressiveness via stimulating pro-tumor activities of tumor-associated macrophages (TAMs). Currently, inhibition of CSF-1/CSF-1R interaction by therapeutic antibody to deplete TAMs and their pro-tumor functions is becoming a prevalent strategy in cancer therapy. However, its antitumor activity shows a limited single-agent effect. Therefore, macrophages in response to M-CSF interruption are pending for further investigation. To achieve this study, bone marrow derived macrophages were generated in vitro by M-CSF stimulation for 7 days and then continuously grown until day 21 in M-CSF absence. A selective pressure for cell survival was initiated after withdrawal of M-CSF. The surviving cells were more prone to M2-like phenotype, even after receiving interleukin-4 (IL-4) stimulation. The transcriptome analysis unveiled that endogenous CSF-1 level was dramatically up-regulated and numerous genes downstream to CSF-1 covering tumor necrosis factor (TNF), ras-related protein 1 (Rap1) and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway were significantly modulated, especially for proliferation, migration and adhesion. Moreover, the phenomenal increase of miR-21-5p and genes related to pro-tumor activity were observed in parallel. In summary, withholding of CSF-1/CSF-1R interaction would rather augment than suspend the M-CSF-driven pro-tumor activities of M2 macrophages in a long run.

scholarly journals The Alternative Faces of Macrophage Generate Osteoclasts

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
N. Lampiasi ◽  
R. Russo ◽  
F. Zito
Keyword(s):  
Macrophage Polarization ◽  
Giant Cells ◽  
Gm Csf ◽  
Receptor Activator ◽  
Inflammatory Stimuli ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Alternatively Activated

The understanding of how osteoclasts are generated and whether they can be altered by inflammatory stimuli is a topic of particular interest for osteoclastogenesis. It is known that the monocyte/macrophage lineage gives rise to osteoclasts (OCs) by the action of macrophage colony stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL), which induce cell differentiation through their receptors, c-fms and RANK, respectively. The multinucleated giant cells (MGCs) generated by the engagement of RANK/RANKL are typical OCs. Nevertheless, very few studies have addressed the question of which subset of macrophages generates OCs. Indeed, two main subsets of macrophages are postulated, the inflammatory or classically activated type (M1) and the anti-inflammatory or alternatively activated type (M2). It has been proposed that macrophages can be polarizedin vitrotowards a predominantly M1 or M2 phenotype with the addition of granulocyte macrophage- (GM-) CSF or M-CSF, respectively. Various inflammatory stimuli known to induce macrophage polarization, such as LPS or TNF-α, can alter the type of MGC obtained from RANKL-induced differentiation. This review aims to highlight the role of immune-related stimuli and factors in inducing macrophages towards the osteoclastogenesis choice.

scholarly journals Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.

1994 ◽  
Vol 179 (4) ◽  
pp. 1109-1118 ◽  
Author(s):  
F Sallusto ◽  
A Lanzavecchia
Keyword(s):  
Mhc Class I ◽  
Tumor Necrosis ◽  
Interleukin 4 ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Necrosis Factor

Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 we have established dendritic cell (DC) lines from blood mononuclear cells that maintain the antigen capturing and processing capacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histocompatibility complex (MHC) class I and class II molecules, CD1, Fc gamma RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones. Their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR-mediated antigen uptake. Incubation of these cultured DCs with tumor necrosis factor alpha (TNF-alpha) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice variant (CD44-v9); by contrast, Fc gamma RII is markedly and sometimes completely downregulated. The functional consequences of the short contact with TNF-alpha are in increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold decrease in presentation of TT-immunoglobulin G complexes.

scholarly journals Recombinant human granulocyte/macrophage colony-stimulating factor enhances monocyte cytotoxicity and secretion of tumor necrosis factor alpha and interferon in cancer patients

Blood ◽  
1989 ◽  
Vol 73 (3) ◽  
pp. 643-646 ◽  
Author(s):  
EJ Wing ◽  
DM Magee ◽  
TL Whiteside ◽  
SS Kaplan ◽  
RK Shadduck
Keyword(s):  
Constant Infusion ◽  
Blood Monocytes ◽  
Necrosis Factor Alpha ◽  
Peripheral Blood Monocytes ◽  
Factor Alpha ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Necrosis Factor

Abstract The colony-stimulating factors (CSFs) promote the proliferation and differentiation of hematopoietic precursors and more recently have been shown to amplify the functions of mature phagocytes in vitro. In this study recombinant human granulocyte/macrophage colony-stimulating factor (rGM-CSF) was administered to cancer patients to determine whether the cytotoxic and secretory activity of their blood monocytes could be enhanced. Patients with refractory neoplastic disease were treated with rGM-CSF either as a single bolus or as a constant infusion for 14 days at either 100 or 500 micrograms/m2 per day. As has been reported by others, the number of peripheral blood monocytes and granulocytes rose markedly in a dose-response fashion during infusion with rGM-CSF. The functional capacity of monocytes was increased by rGM- CSF, since the cytotoxicity of monocytes against antibody-coated xenogeneic cells was increased during the constant infusion compared to baseline. In addition, monocytes harvested during the constant infusion and stimulated with lipopolysaccharide (LPS) in vitro secreted increased quantities of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN). These data indicate that rGM-CSF can enhance both the number and the function of peripheral blood monocytes in vivo.

scholarly journals Effects of Granulocyte-Macrophage Colony-Stimulating Factor and Tumor Necrosis Factor Alpha on Trypanosoma cruzi Trypomastigotes

1998 ◽  
Vol 66 (6) ◽  
pp. 2722-2727 ◽  
Author(s):  
Elizabeth Olivares Fontt ◽  
Patrick De Baetselier ◽  
Carlo Heirman ◽  
Kris Thielemans ◽  
Ralph Lucas ◽  
...  
Keyword(s):  
Necrosis Factor Alpha ◽  
Gm Csf ◽  
Tnf Α ◽  
No Release ◽  
Factor Alpha ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Necrosis Factor

ABSTRACT We have previously shown that the addition of exogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) to nonactivated mouse peritoneal macrophages (MPM) limitsTrypanosoma cruzi infections in vitro (E. Olivares Fontt and B. Vray, Parasite Immunol. 17:135–141, 1995). Lower levels of infection were correlated with a higher level of production of tumor necrosis factor alpha (TNF-α) in the absence of nitric oxide (NO) release. These data suggested that GM-CSF and/or TNF-α might have a direct parasitocidal effect on T. cruzi trypomastigotes, independently of NO release. To address this question, T. cruzi trypomastigotes were treated with recombinant murine GM-CSF (rmGM-CSF), recombinant murine TNF-α (rmTNF-α), or both cytokines in a cell-free system. Treatment with rmGM-CSF but not rmTNF-α caused morphological changes in the parasites, and most became spherical after 7 h of incubation. Both cytokines exerted a cytolytic activity on the trypomastigotes, yet the trypanolytic activity of rmTNF-α was more effective than that of rmGM-CSF. Viable rmGM-CSF- and rmTNF-α-treated parasites were less able to infect MPM than untreated parasites, and this reduction in infectivity was greatest for rmGM-CSF. Treatments with both cytokines resulted in more lysis and almost complete inhibition of infection. The direct parasitocidal activity of rmTNF-α was inhibited by carbohydrates and monoclonal antibodies specific for the lectin-like domain of TNF-α. Collectively, these results suggest that cytokines such as GM-CSF and TNF-α may directly control the level of T. cruzi trypomastigotes at least in vitro and so could determine the outcome of infection in vivo.

Induction of osteoclasts from CD14-positive human peripheral blood mononuclear cells by receptor activator of nuclear factor κB ligand (RANKL)

2000 ◽  
Vol 99 (2) ◽  
pp. 133-140 ◽  
Author(s):  
Geoffrey C. NICHOLSON ◽  
Mary MALAKELLIS ◽  
Fiona M. COLLIER ◽  
Paul U. CAMERON ◽  
Wayne R. HOLLOWAY ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Human Macrophage ◽  
Peripheral Blood Mononuclear ◽  
Receptor Activator ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Necrosis Factor

Osteoclasts are bone-resorbing cells that are derived from haemopoietic precursors, including cells present in peripheral blood. The recent identification of RANKL [receptor activator of nuclear factor (NF)-κB ligand], a new member of the tumour necrosis factor ligand superfamily that has a key role in osteoclastogenesis, has allowed the in vitro generation of osteoclasts in the absence of cells of the stromal/osteoblast lineage. Human peripheral blood mononuclear cells (PBMC) cultured in vitro with soluble RANKL and human macrophage colony-stimulating factor form osteoclasts. However, PBMC are heterogeneous, consisting of subsets of monocytes and lymphocytes as well as other blood cells. As the CD14 marker is strongly expressed on monocytes, the putative osteoclast precursor in peripheral blood, we have selected CD14+ cells from PBMC to examine their osteoclastogenic potential and their expression of novel members of the tumour necrosis factor superfamily involved in osteoclastogenesis. Highly purified CD14+ cells demonstrated mRNA expression of receptor activator of NF-κB, but no expression of RANKL or osteoprotegerin, whereas PBMC expressed mRNAs for all three factors. CD14+ (but not CD14-) cells cultured on bone slices for 21 days with human macrophage colony-stimulating factor and soluble RANKL generated osteoclasts and showed extensive bone resorption. Similar numbers of osteoclasts were generated by 105 CD14+ cells and 106 PBMC, but there was significantly less intra-assay variability with CD14+ cells, suggesting the absence of stimulatory/inhibitory factors from these cultures. The ability of highly purified CD14+ cells to generate osteoclasts will facilitate further characterization of the phenotype of circulating osteoclast precursors and cell interactions in osteoclastogenesis.

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