Effects of macrophage colony-stimulating factor on microglial responses to lipopolysaccharide and beta amyloid

Vidyadaran, Sharmili; Ooi, Yin Yin; Subramaiam, Hemavathy; Badiei, Alireza; Abdullah, Maha; Ramasamy, Rajesh; Seow, Heng Fong

doi:10.1016/j.cellimm.2009.06.005

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…Upon exposure to lipopolysaccharide (LPS), microglia secrete inflammatory mediators and upregulate expression of major histocompatibility complex (MHC) class II receptors and CD40 to facilitate antigen presentation to T lymphocytes [19]. Due to these effects, LPS is a common stimulus for activating microglia in vitro [20-22], including for our previous work [23-25]. …”

Section: Resultsmentioning

confidence: 99%

“…LPS is a bacterial cell wall component that triggers microglia activation via Toll-like receptor 4 [19]. With 1 μg/ml LPS, a dose routinely used to activate microglia in conventional monolayer cultures [20,24,25], BV2 microglia in 3D cultures significantly increased expression of the cell surface receptor CD40, nitric oxide (NO), IL-6, TNF-α and MCP-1 . This demonstrates that both cells and supernatant of 3D collagen cultures can be assayed, demonstrating the suitability of this culture system to accommodate a range of tests.…”

Section: Discussionmentioning

confidence: 99%

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A three-dimensional collagen construct to model lipopolysaccharide-induced activation of BV2 microglia

Haw

Tong

Yew

et al. 2014

J Neuroinflammation

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BackgroundWe report a novel method of culturing microglia in three dimension (3D) using collagen as a substrate. By culturing microglia within a matrix, we aim to emulate the physical state of microglia embedded within parenchyma.MethodsBV2 microglia cell suspensions were prepared with type I collagen and cast into culture plates. To characterise the BV2 microglia cultured in 3D, the cultures were evaluated for their viability, cell morphology and response to lipopolysaccharide (LPS) activation. Conventional monolayer cultures (grown on uncoated and collagen-coated polystyrene) were set up concurrently for comparison.ResultsBV2 microglia in 3D collagen matrices were viable at 48 hrs of culture and exhibit a ramified morphology with multiplanar cytoplasmic projections. Following stimulation with 1 μg/ml LPS, microglia cultured in 3D collagen gels increase their expression of nitric oxide (NO) and CD40, indicating their capacity to become activated within the matrix. Up to 97.8% of BV2 microglia grown in 3D cultures gained CD40 positivity in response to LPS, compared to approximately 60% of cells grown in a monolayer (P < .05). BV2 microglia in 3D collagen gels also showed increased mRNA and protein expression of inflammatory cytokines IL-6, TNF-α and the chemoattractant MCP-1 following LPS stimulation.ConclusionsIn summary, BV2 microglia cultured in 3D collagen hydrogels exhibit multiplanar cytoplasmic projections and undergo a characteristic and robust activation response to LPS. This culture system is accessible to a wide range of analyses and provides a useful new in vitro tool for research into microglial activation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A three-dimensional collagen construct to model lipopolysaccharide-induced activation of BV2 microglia

Haw

Tong

Yew

et al. 2014

J Neuroinflammation

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“…The immortalised microglia cell line BV2 [52], shares properties with body macrophages with respect to the antigen profile, phagocytic capacity and antimicrobial activity [55]. The bacterial endotoxin LPS was used to activate microglia at a dose previously shown to stimulate microglia into an activated phenotype [26,[56][57][58][59] without affecting cell viability.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow-derived mesenchymal stem cells modulate BV2 microglia responses to lipopolysaccharide

Ooi

Ramasamy

Rahmat

et al. 2010

International Immunopharmacology

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“…Signaling through the M-CSF receptor (CSF-1R) is required for the development and differentiation of microglia [15] and M-CSF has been shown to increase division of rodent and human fetal microglia [14,16,17]. M-CSF also has the ability to change microglial morphology [18,19] and influence microglial activation [20,21].…”

Section: Introductionmentioning

confidence: 99%

M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

Smith

Gibbons

Oldfield³

et al. 2013

J Neuroinflammation

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BackgroundMicroglia are the primary immune cells of the brain whose phenotype largely depends on their surrounding micro-environment. Microglia respond to a multitude of soluble molecules produced by a variety of brain cells. Macrophage colony-stimulating factor (M-CSF) is a cytokine found in the brain whose receptor is expressed by microglia. Previous studies suggest a critical role for M-CSF in brain development and normal functioning as well as in several disease processes involving neuroinflammation.MethodsUsing biopsy tissue from patients with intractable temporal epilepsy and autopsy tissue, we cultured primary adult human microglia to investigate their response to M-CSF. Mixed glial cultures were treated with 25 ng/ml M-CSF for 96 hours. Proliferation and phagocytosis assays, and high through-put immunocytochemistry, microscopy and image analysis were performed to investigate microglial phenotype and function.ResultsWe found that the phenotype of primary adult human microglia was markedly changed following exposure to M-CSF. A greater number of microglia were present in the M-CSF- treated cultures as the percentage of proliferating (BrdU and Ki67-positive) microglia was greatly increased. A number of changes in protein expression occurred following M-CSF treatment, including increased transcription factors PU.1 and C/EBPβ, increased DAP12 adaptor protein, increased M-CSF receptor (CSF-1R) and IGF-1 receptor, and reduced HLA-DP, DQ, DR antigen presentation protein. Furthermore, a distinct morphological change was observed with elongation of microglial processes. These changes in phenotype were accompanied by a functional increase in phagocytosis of Aβ1-42 peptide.ConclusionsWe show here that the cytokine M-CSF dramatically influences the phenotype of adult human microglia. These results pave the way for future investigation of M-CSF-related targets for human therapeutic benefit.

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Effects of macrophage colony-stimulating factor on microglial responses to lipopolysaccharide and beta amyloid

Cited by 8 publications

References 34 publications

A three-dimensional collagen construct to model lipopolysaccharide-induced activation of BV2 microglia

A three-dimensional collagen construct to model lipopolysaccharide-induced activation of BV2 microglia

Bone marrow-derived mesenchymal stem cells modulate BV2 microglia responses to lipopolysaccharide

M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

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