Inhibition of microglia multinucleated giant cell formation and induction of differentiation by GM-CSF using a porcine in vitro model

Tambuyzer, Bart; Nouwen, Etienne J.

doi:10.1016/j.cyto.2005.05.006

Cited by 28 publications

(27 citation statements)

References 38 publications

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“…1e and f). These cells have also been shown to be CD11b + , bind lectin GS-Ib4, and stain for acid phosphatase and nonspecific esterase [4,9].…”

Section: Phenotypic Characterization Of Microgliamentioning

confidence: 96%

“…Mixed glial cortical and microglial cultures from newborn pigs were set up as described earlier [4]. Cell cultures were fixed and labeled using a mouse antiporcine CD45 ab (1 : 20; Serotec, Kidlington, Oxford, UK), followed by labeling with a horse antimouse biotinylated secondary ab (1 : 200) and an avidin-biotin-horse radish peroxidase complex (both from Vector Laboratories, Burlingame, California, USA).…”

Section: Mixed Glial and Microglial Cultures: Phenotypic Characterizamentioning

confidence: 99%

“…These activated cells not only eliminate pathogens [2], but also necrotic neurons and glia within lesioned brain areas [3]. Activated microglia secrete a broad spectrum of molecules such as cytokines, chemokines, and reactive oxygen (ROS)/nitrogen species [4,5]. Moreover, phagocytosis itself can induce the production of free radicals necessary for efficient degradation of ingested material [6].…”

Section: Introductionmentioning

confidence: 98%

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Interferon-γ modulates the functional profile of in-vitro-cultured porcine microglia

Tambuyzer

Casteleyn²,

Cruchten³

et al. 2012

NeuroReport

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Microglia are the most important immune cells within the highly specialized environment of the central nervous system. Upon activation, they transform from a resting 'ramified' into a fully functional 'amoeboid' phenotype with the ability to perform phagocytosis and generate free radicals. A combined flow cytometric assay for the simultaneous measurement of these two functions in porcine microglia in vitro is presented: reactive oxygen species are detected using hydroethidine; phagocytosis is assessed using fluorescein isothiocyanate-labeled latex beads. The combination of these two probes allowed us to distinguish four subpopulations within cultured porcine microglia on the basis of their functional activity. The effect of several exogenous stimuli [phorbol myristate acetate, conditioned medium, interferon γ (IFN-γ)] on the in-vitro functional properties of porcine microglia is investigated using this test. In particular for IFN-γ, a significant modulatory effect on the intracellular reactive oxygen species production and phagocytic activity was observed. This result suggests an alternative role of IFN-γ acting on cultured porcine microglia.

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“…1e and f). These cells have also been shown to be CD11b + , bind lectin GS-Ib4, and stain for acid phosphatase and nonspecific esterase [4,9].…”

Section: Phenotypic Characterization Of Microgliamentioning

confidence: 96%

Section: Mixed Glial and Microglial Cultures: Phenotypic Characterizamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Interferon-γ modulates the functional profile of in-vitro-cultured porcine microglia

Tambuyzer

Casteleyn²,

Cruchten³

et al. 2012

NeuroReport

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“…While previous studies have found that PMA stimulation of microglia cells leads to an increase in ROS generation, the human cells in the study by Hu et al [22] appear to have some baseline ROS generation. Further, the ability of PMA to stimulate ROS generation in porcine microglia changes significantly during the first 4 days in culture [23] , and can be modified by treatment with cytokines [22,23] . Thus, it appears that, as in other properties of microglia, the profile of NOX isoforms and ROS generation is dependent on the state of the cell, and that NOX2 may not be the only isoform at play, and in fact may not be present at all in the resting state [9,10] .…”

Section: Discussionmentioning

confidence: 99%

NOX4 Expression in Human Microglia Leads to Constitutive Generation of Reactive Oxygen Species and to Constitutive IL-6 Expression

Bedard

Sorce

et al. 2009

J Innate Immun

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pression of the microglia-typical genes MHCII, CD68 and CD11b, nor did it affect the expression of iNOS, VEGF or TGF-␤ . However, there was a marked decrease in IL-6 mRNA. Taken together, we demonstrate a constitutive NOX4-dependent ROS generation in a microglial cell line which leads to expression of IL-6 mRNA. The possibility that microglia could switch from tightly regulated NOX2-dependent ROS generation to constitutive NOX4-dependent ROS generation is of interest for the understanding of the role of microglia in maintaining the balance between neuroprotection and neuroinflammatory damage.

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“…Helming and Gordon (2007) proposed that MGC formation in a granuloma could be induced by the cytokines and signals derived from bacteria, parasites or other foreign materials and that this local environment induces expression of fusogenic factors; therefore, the induction or modulation of MGC formation may be enhanced or suppressed depending on the cytokines present during the initial stimulus. In addition to IFN-γ other pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and granulocyte macrophage col- ony-stimulating factor (GM-CSF) have been employed in the in vitro generation of MGC (Gasser & Most 1999, Tambuyzer & Nouwen 2005.…”

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confidence: 99%

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

Bannwart

Nakaira-Takahagi

Peraçoli

2011

Mem. Inst. Oswaldo Cruz

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Multinucleated giant cells (MGC) are cells present in characteristic granulomatous inflammation induced by intracellular infectious agents or foreign materials. The present study evaluated the modulatory effect of granulocyte macrophage colony-stimulating factor (GM-CSF) in association with other cytokines such as interferon-gamma (IFN-γ), tumour necrosis factor-alpha, interleukin (IL)-10 or transforming growth factor beta (TGF-β1) on the formation of MGC from human peripheral blood monocytes stimulated with Paracoccidioides brasiliensis antigen (PbAg). The generation of MGC was determined by fusion index (FI) and the fungicidal activity of these cells was evaluated after 4 h of MGC co-cultured with viable yeast cells of P. brasiliensis strain 18 (Pb18). The results showed that monocytes incubated with PbAg and GM-CSF plus IFN-γ had a significantly higher FI than in all the other cultures, while the addition of IL-10 or TGF-β1 had a suppressive effect on MGC generation. Monocytes incubated with both pro and anti-inflammatory cytokines had a higher induction of foreign body-type MGC rather than Langhans-type MGC. MGC stimulated with PbAg and GM-CSF in association with the other cytokines had increased fungicidal activity and the presence of GM-CSF also partially inhibited the suppressive effects of IL-10 and TGF-β1. Together, these results suggest that GM-CSF is a positive modulator of PbAg-stimulated MGC generation and on the fungicidal activity against Pb18

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Inhibition of microglia multinucleated giant cell formation and induction of differentiation by GM-CSF using a porcine in vitro model

Cited by 28 publications

References 38 publications

Interferon-γ modulates the functional profile of in-vitro-cultured porcine microglia

Interferon-γ modulates the functional profile of in-vitro-cultured porcine microglia

NOX4 Expression in Human Microglia Leads to Constitutive Generation of Reactive Oxygen Species and to Constitutive IL-6 Expression

Granulocyte macrophage colony-stimulating factor enhances the modulatory effect of cytokines on monocyte-derived multinucleated giant cell formation and fungicidal activity against Paracoccidioides brasiliensis

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