Factors regulating macrophage production and growth: identity of colony-stimulating factor and macrophage growth factor.

Stanley, E. Richard; Cifone, Maria A.; Heard, P M; Defendi, V.

doi:10.1084/jem.143.3.631

Cited by 245 publications

(71 citation statements)

References 40 publications

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“…Bone marrow-derived macrophages (BMMs) and DCs were generated by M-CSF containing L cell conditioned media (40) and GM-CSF containing media from X63 Ag8 cells (41), respectively. Cells were stimulated with plate-coated compounds.…”

Section: Generation and Stimulation Of Bone Marrow-derived Macrophagementioning

confidence: 99%

Differential Control of Mincle-Dependent Cord Factor Recognition and Macrophage Responses by the Transcription Factors C/EBPβ and HIF1α

Schoenen

Huber

Sonda

et al. 2014

The Journal of Immunology

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Trehalose-6,6-dimycolate (TDM), the mycobacterial cord factor, and its synthetic analog Trehalose-6,6-dibehenate (TDB) bind to the C-type lectin receptors macrophage-inducible C-type lectin (Mincle) and Mcl to activate macrophages. Genetically, the transcriptional response to TDB/TDM has been defined to require FcRγ-Syk-Card9 signaling. However, TDB/TDM-triggered kinase activation has not been studied well, and it is largely unknown which transcriptional regulators bring about inflammatory gene expression. In this article, we report that TDB/TDM caused only weak Syk-phosphorylation in resting macrophages, consistent with low basal Mincle expression. However, LPS-priming caused MYD88-dependent upregulation of Mincle, resulting in enhanced TDB/TDM-induced kinase activation and more rapid inflammatory gene expression. TLR-induced Mincle expression partially circumvented the requirement for Mcl in the response to TDB/TDM. To dissect transcriptional responses to TDB/TDM, we mined microarray data and identified early growth response (Egr) family transcription factors as direct Mincle target genes, whereas upregulation of Cebpb and Hif1a required new protein synthesis. Macrophages and dendritic cells lacking C/EBPβ showed nearly complete abrogation of TDB/TDM responsiveness, but also failed to upregulate Mincle. Retroviral rescue of Mincle expression in Cebpb-deficient cells restored induction of Egr1, but not of G-CSF. This pattern of C/EBPβ dependence was also observed after stimulation with the Dectin-1 ligand Curdlan. Inducible expression of hypoxia-inducible factor 1α (HIF1α) also required C/EBPβ. In turn, HIF1α was not required for Mincle expression, kinase activation, and Egr1 or Csf3 expression, but critically contributed to NO production. Taken together, we identify C/EBPβ as central hub in Mincle expression and inflammatory gene induction, whereas HIF1α controls Nos2 expression. C/EBPβ also connects TLR signals to cord factor responsiveness through MYD88-dependent upregulation of Mincle.

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Section: Generation and Stimulation Of Bone Marrow-derived Macrophagementioning

confidence: 99%

Differential Control of Mincle-Dependent Cord Factor Recognition and Macrophage Responses by the Transcription Factors C/EBPβ and HIF1α

Schoenen

Huber

Sonda

et al. 2014

The Journal of Immunology

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“…PC-PLC activity is precipitated by anti-phosphotyrosine antibodies following activation of CSF-1R, indicating that tyrosine phosphorylation is associated with PC-PLC activation in a manner similar to that observed for phosphatidylinositol 3'-kinase and phospholipase Cyl (11). However, deletion of the kinase insert region from CSF-1R does not diminish the extent of CSF-1-activated PtdCho hydrolysis, indicating that a different region of the receptor is involved in transducing the signal to PC-PLC (12 (65) and used as the source of CSF-1 for routine growth and maintenance of the BAC1.2F5 cell line. Antibody to the CSF-1 receptor (29) was kindly provided by Jim Downing, and polyclonal antiphosphotyrosine antibody (33) was provided by Albert Reynolds.…”

mentioning

confidence: 99%

Phosphatidylcholine hydrolysis and c-myc expression are in collaborating mitogenic pathways activated by colony-stimulating factor 1.

Xu¹,

Tessner²,

Rock³

et al. 1993

Mol. Cell. Biol.

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Stimulation of diglyceride production via phospholipase C (PLC) hydrolysis of phosphatidylcholine was an early event in the mitogenic action of colony-stimulating factor 1 (CSF-1) in the murine macrophage cell line BAC1.2F5 and was followed by a second phase of diglyceride production that persisted throughout the G1 phase of the cell cycle. Addition of phosphatidylcholine-specific PLC (PC-PLC) from Bacillus cereus to the medium of quiescent cells raised the intracellular diglyceride concentration and stimulated [3H]thymidine incorporation, although PC-PLC did not support continuous proliferation. PC-PLC treatment did not induce tyrosine phosphorylation or turnover of the CSF-1 receptor. The major protein kinase C (PKC) isotype in BAC1.2F5 cells was PKC-delta. Diglyceride production from PC-PLC did not target PKC-delta, since unlike phorbol esters, PC-PLC treatment neither decreased the electrophoretic mobility of PKC-delta nor increased the amount of GTP bound to Ras, and PC-PLC was mitogenically active in BAC1.2F5 cells in which PKC-delta was downregulated by prolonged treatment with phorbol ester. PC-PLC mimicked CSF-1 action by elevating c-fos and junB mRNAs to 40% of the level induced by CSF-1; however, PC-PLC induced c-myc mRNA to only 5% of the level in CSF-1-stimulated cells. PC-PLC addition to CSF-1-dependent BAC1.2F5 clones that constitutively express c-myc increased [3H]thymidine incorporation to 86% of the level evoked by CSF-1 and supported slow growth in the absence of CSF-1. Therefore, PC-PLC is a component of a signal transduction pathway leading to transcription of c-fos and junB that collaborates with c-myc and is independent of PKC-delta and Ras activation.

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“…When the most recent classification for mononuclear phagocytes was proposed (31), there was no need to provide for cells with selfreplicating properties not localized in the bone marrow. Clearly, we and others (3,(7)(8)(9) have accumulated ample evidence to show that these peripheral cells can replicate. Therefore, the proposed classification should be changed to include these precursor cells which, though derived from the bone marrow, retain an extensive self-replicating potential when they infiltrate peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

Proliferative capacity of mouse peritoneal macrophages in vitro.

Zeijst¹,

Stewart²,

Schlesinger³

1978

The Journal of Experimental Medicine

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Thioglycolate-stimulated mouse peritoneal macrophages cultured in the presence of macrophage growth factor (MGF) will continue to proliferate when they are removed from culture dishes with the local anesthetic lidocaine and subcultured. The number of times the cells can be subcultured and remain in a proliferative state is dependent on the number of previous cell divisions. One precursor cell (colony-forming cell) yields about 2.6 X 10(4) daughter cells. When MGF is removed from actively proliferating macrophages, they leave the cell cycle and enter a "resting" condition. When MGF is readded, cells reenter the cell cycle and proliferate with the same doubling time as if MGF had not been removed. Membrane 5'-nucleotidase activity was used as a probe to identify the state of macrophage activation. Proliferating macrophage populations had significantly higher enzyme levels than stimulated macrophages cultured without MGF. These enzymes levels were, however, lower than those found for resident (unstimulated) macrophages.

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Factors regulating macrophage production and growth: identity of colony-stimulating factor and macrophage growth factor.

Cited by 245 publications

References 40 publications

Differential Control of Mincle-Dependent Cord Factor Recognition and Macrophage Responses by the Transcription Factors C/EBPβ and HIF1α

Differential Control of Mincle-Dependent Cord Factor Recognition and Macrophage Responses by the Transcription Factors C/EBPβ and HIF1α

Phosphatidylcholine hydrolysis and c-myc expression are in collaborating mitogenic pathways activated by colony-stimulating factor 1.

Proliferative capacity of mouse peritoneal macrophages in vitro.

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