End-stage dying glioma cells are engulfed by mouse microglia with a strain-dependent efficacy

Nickles, Dorothee; Abschuetz, Anette; Zimmer, Heiko; Kees, Tim; Geibig, Renate; Spieß, Eberhard; Régnier‐Vigouroux, Anne

doi:10.1016/j.jneuroim.2008.03.022

Cited by 12 publications

(9 citation statements)

References 43 publications

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“…demonstrated active phagocytosis of beads by MP isolated from fresh GBM samples ex vivo (13). Similarly, Nickles et al showed phagocytosis of apoptotic glioma cells by activated MP in vitro (14). Our findings also suggest that TAM can efficiently phagocytize foreign particles, possibly indicating an intact pro-inflammatory function.…”

Section: Discussionmentioning

confidence: 92%

“…In CNS inflammatory conditions, activated MG and MP release pro-inflammatory cytokines and become capable of phagocytosis and antigen presentation (8). Several studies have also confirmed an intact MP phagocytic function in gliomas (13, 14). These findings suggest that TAMs are still capable of phagocytosis and could potentially be employed as nanoparticle carriers into brain tumors.…”

Section: Introductionmentioning

confidence: 83%

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Tumor-associated macrophages are predominant carriers of cyclodextrin-based nanoparticles into gliomas

Alizadeh

Zhang

Hwang

et al. 2010

Nanomedicine: Nanotechnology, Biology and Medicine

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The goal of this study was to evaluate the mechanism of cyclodextrin-based nanoparticle (CDP-NP) uptake into a murine glioma model. Using mixed in vitro culture systems, we demonstrated that CDP-NP was preferentially taken up by BV2 and N9 microglia (MG) cells as compared to GL261 glioma cells. Fluorescent microscopy and flow cytometry analysis of intracranial (i.c.) GL261 gliomas confirmed these findings and demonstrated a predominant CDP-NP uptake by macrophages (MP) and MG within and around the tumor site. Interestingly, in mice bearing bilateral i.c. tumor, MG and MP carrying CDP-NP were able to migrate to the contralateral tumors. In conclusion, these studies better characterize the cellular distribution of CDP-NP in i.c. tumors and demonstrate that MP and MG could potentially be used as nanoparticle drug carriers into malignant brain tumors.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 83%

Tumor-associated macrophages are predominant carriers of cyclodextrin-based nanoparticles into gliomas

Alizadeh

Zhang

Hwang

et al. 2010

Nanomedicine: Nanotechnology, Biology and Medicine

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“…Microscopic observation showed that the two glioma cell lines SMA-560 and MT539MG were killed by primary culture of VM/Dk microglia stimulated with a combination of LPS and IFN-g in a co-culture setting (Nickles et al, 2008) or after incubation with culture supernatant of the stimulated microglia (SN1) (Fig. 1A).…”

Section: Tnf-a and Tumor Necrosis Factor-related Apoptosis-inducing Lmentioning

confidence: 99%

TNF‐α‐ and TRAIL‐resistant glioma cells undergo autophagy‐dependent cell death induced by activated microglia

Mora

Abschuetz

Kees

et al. 2008

Glia

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The role of microglia, the brain resident macrophages, in glioma biology is still ill-defined. Despite their cytotoxic potential, these cells that significantly infiltrate the tumor mass seem to support tumor growth rather than tumor eradication. A proper activation of microglia anti-tumor activities within the tumor may provide a valuable additional arm of defense to immunotherapies against brain tumors. We herewith report a detailed characterization of (lipopolysaccharide and interferon-gamma)-induced anti-tumor activities of mouse primary microglia towards two TNF-alpha and TRAIL resistant glioma cell lines, in cell monolayer or spheroid cultures and in collagen-embedded tumor explants. Irrespective of the mouse strain, stimulated microglia secreted proteic factors that decreased proliferation and migration of these glioma cells and efficiently killed them. Death occurred specifically in glioma cells as demonstrated by the lack of toxicity of microglia supernatant towards primary cultures of astrocytes or neurons. Cell death was characterized by the early accumulation of acidic vesicles, phosphatidylserine exposure, appearance of double-membrane cytoplasmic vesicles, extensive zeiosis and a very late loss of DNA in cells that had lost membrane integrity. Inhibition of autophagosome formation efficiently protected glioma cells from death whereas caspase inhibition could only prevent DNA loss but not cytotoxicity. Death however, resulted from a blockade by microglia supernatant of the basal autophagic flux present in the glioma cells. These observations demonstrate that glioma cells resistant to apoptotic death ligands could be successfully and specifically killed through autophagy-dependent death induced by appropriately activated microglia.

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“…Studies have also shown strain-dependent differences in microglial inflammatory properties in vitro either in cell lines or primary microglial cells (McLaughlin et al 2006; Nickles et al 2008; Wei and Lin 2009). A comparison of the vast literature on BV-2 and N9 cells, the most commonly used microglial cell lines, suggests dissimilarities in their immune responsiveness (Baker et al 2004; Fleisher-Berkovich et al 2010; Horigome et al 1994; Susaki et al 1996; Zhang et al 2003).…”

mentioning

confidence: 99%

Outbred ICR/CD1 mice display more severe neuroinflammation mediated by microglial TLR4/CD14 activation than inbred C57Bl/6 mice

Nikodémová

Watters

2011

Neuroscience

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Neuroinflammation mediated by microglia is a pathological hallmark of many CNS disorders. Cell lines derived from inbred C57Bl/6 and outbred ICR/CD1 mice (BV2 and N9 respectively), are often used to study microglial inflammatory activities. Although many studies demonstrate different responses of these cell lines to the same stimulus, no comparisons have been done in vivo. Because inbreeding reduces resistance to pathogens and parasites, we hypothesized that microglia from outbred ICR/CD1 mice would have a stronger response to centrally administered LPS than microglia from inbred C57Bl/6 mice. The evaluation of gene expression in freshly-isolated CD11b+ cells from brain revealed that microglia from ICR/CD1 mice were more pro-inflammatory than those from C57Bl/6 mice, although these differences did not appear to result from alterations in the expression levels of the LPS receptors TLR4 or CD14. Notably, the timing of inflammatory gene expression did not correlate with CD11b+ cell proliferation/infiltration. The highest expression of TNFα, IL-6 and iNOS occurred 3 hours after LPS injection when the number of CD11b+ cells was not changed. Whereas the expression of these pro-inflammatory genes had returned to basal by 48 hours when the highest number of CD11b+ cells in the brain was found, the expression of the anti-inflammatory cytokine IL-10 was still significantly up-regulated. This is important because the increased presence of CD11b+ cells in the CNS is often used as an indicator of neuroinflammation. While LPS did not affect the expression of the growth factors VEGF or BDNF, we observed that mechanical injury (caused by intraparenchymal injection) induced distinct patterns of microglial activation characterized by increased expression of VEGF and down-regulation of BDNF. It remains to be determined which type of microglia is more beneficial/detrimental to the CNS, but our data suggest that genetic traits determining microglial properties may have profound effect on many CNS pathologies.

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End-stage dying glioma cells are engulfed by mouse microglia with a strain-dependent efficacy

Cited by 12 publications

References 43 publications

Tumor-associated macrophages are predominant carriers of cyclodextrin-based nanoparticles into gliomas

Tumor-associated macrophages are predominant carriers of cyclodextrin-based nanoparticles into gliomas

TNF‐α‐ and TRAIL‐resistant glioma cells undergo autophagy‐dependent cell death induced by activated microglia

Outbred ICR/CD1 mice display more severe neuroinflammation mediated by microglial TLR4/CD14 activation than inbred C57Bl/6 mice

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