Modeling CNS microglia: the quest to identify predictive models

Crane, Janelle; Xie, Alison Xiaoqiao

doi:10.1016/j.ddmod.2008.07.006

Cited by 31 publications

(16 citation statements)

References 33 publications

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“…We previously reported that cultured microglia are only in part predictive of microglial responses in vivo (Carson et al 1998, Carson et al 2008, Schmid et al 2009). Therefore, we examined whether direct intracerebral injection of LPS/IFNγ led to an increase in ODC expression in the CNS as revealed by 33 P-labeled riboprobe exposure of autoradiograms.…”

Section: Resultsmentioning

confidence: 99%

LPS-induced CCL2 expression and macrophage influx into the murine central nervous system is polyamine-dependent

Puntambekar¹,

Davis²,

Hawel³

et al. 2011

Brain, Behavior, and Immunity

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Increased polyamine production is observed in a variety of chronic neuroinflammatory disorders, but in vitro and in vivo studies yield conflicting data on the immunomodulatory consequences of their production. Ornithine decarboxylase (ODC) is the rate-limiting enzyme in endogenous polyamine production. To identify the role of polyamine production in CNS-intrinsic inflammatory responses, we defined CNS sites of ODC expression and the consequences of inhibiting ODC in response to intracerebral injection of LPS+/− IFNγ. In situ hybridization analysis revealed that both neurons and non-neuronal cells rapidly respond to LPS+/− IFNγ by increasing ODC expression. Inhibiting ODC by co-injecting DFMO decreased LPS-induced CCL2 expression and macrophage influx into the CNS, without altering LPS-induced microglial or macrophage activation. Conversely, intracerebral injection of polyamines was sufficient to trigger macrophage influx into the CNS of wild-type but not CCL2KO mice, demonstrating the dependence of macrophage influx on CNS expression of CCL2. Consistent with these data, addition of putrescine and spermine to mixed glial cultures dramatically increased CCL2 expression and to a much lesser extent, TNF expression. Addition of all three polyamines to mixed glial cultures also decreased the numbers and percentages of oligodendrocytes present. However, in vivo, inhibiting the basal levels of polyamine production was sufficient to induce expression of apolipoprotein D, a marker of oxidative stress, within white matter tracts. Considered together, our data indicate that: (1) CNS-resident cells including neurons play active roles in recruiting pro-inflammatory TREM1+ macrophages into the CNS via polyamine-dependent induction of CCL2 expression and (2) modulating polyamine production in vivo may be a difficult strategy to limit inflammation and promote repair due to the dual homeostatic and pro-inflammatory roles played by polyamines.

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Section: Resultsmentioning

confidence: 99%

LPS-induced CCL2 expression and macrophage influx into the murine central nervous system is polyamine-dependent

Puntambekar¹,

Davis²,

Hawel³

et al. 2011

Brain, Behavior, and Immunity

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“…In addition to the effects of catecholamines in modulating macrophage immune responses, recent studies have shown that macrophages can potently affect the central nervous system (CNS), demonstrating that bi-directional communication exists in these neural immune circuits [27, 28]. Like all tissues in the body, the CNS has a resident population of macrophages.…”

Section: Catecholaminesmentioning

confidence: 99%

“…Chronic activation of microglia as can lead to dysregulated and/or neurotoxic functions contributing to neurodegeneration, neuropathic pain and/or decreased cognitive ability. Most studies have focused on the role of pathogen associated molecular patterns (PAMP) or danger associated molecular pattern (DAMP) molecules as the primary signals triggering maladaptive microglial activation in CNS injury and disease function [27, 28]. However, in vitro and in vivo studies now reveal that norephinephrine (NE) plays a non-redundant and complementary role to DAMP and PAMP signals.…”

Section: Catecholaminesmentioning

confidence: 99%

Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system

2015

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Catecholamines and adipokines function as hormones; catecholamines as neurotransmitters in the sympathetic nervous system, and adipokines as mediators of metabolic processes. It has become increasingly clear, however, that both also function as immunomodulators of innate and adaptive immune cells, including macrophages. Macrophages can respond to, as well as produce their own catecholamines. Dopamine, noradrenaline, and adrenaline are the most abundant catecholamines in the body, and can induce both pro-inflammatory and anti-inflammatory immune responses in macrophages, as well as non-immune processes such as thermogenesis. Though they are responsive to adipokines, particularly lipoproteins, leptin, and adiponectin, macrophages generally do synthesize their own adipokines, with the exception being resistin-like molecules. Adipokines contribute to adverse metabolic and immune response by stimulating lipid accumulation, foam cell formation and pro-inflammatory cytokine production in macrophages. Adipokines can also promote balance or resolution during metabolic and immune processes by promoting reverse lipid transport and expression of Th2 cytokines. This review will explore the mechanisms by which catecholamines and adipokines influence macrophage function in neural pathways, immunity and metabolism.

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“…44 For example, microglia are the resident tissue macrophages of the central nervous system. 6 Macrophages are the first to mediate host immune responses against foreign objects. In addition to their role as eliminators of invading pathogens, macrophages can also release growth factors, cytokines, interleukins, and nitric oxide that trigger other inflammatory responses and mediate repair of damaged tissues.…”

Section: Macrophages As Vectors For the Delivery Of Nanoshellsmentioning

confidence: 99%

Macrophages as Cell-Based Delivery Systems for Nanoshells in Photothermal Therapy

et al. 2011

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Site-specific delivery of nanoparticles poses a significant challenge, especially in the brain where the blood–brain barrier prevents the entry of most therapeutic compounds including nanoparticle-based anti-cancer agents. In this context, the use of macrophages as vectors for the delivery of gold–silica nanoshells to infiltrating gliomas will be reviewed in this article. Gold–silica nanoshells are readily phagocytosed by macrophages without any apparent toxic effects, and the results of in vitro studies have demonstrated the migratory potential of nanoshell-loaded macrophages in human glioma spheroids. Of particular interest is the observation that, after near-infrared exposure of spheroids containing nanoshell-loaded macrophages, sufficient heat was generated to suppress spheroid growth. Collectively, these findings demonstrate the potential of macrophages as nanoshell delivery vectors for photothermal therapy of gliomas, and they certainly provide the basis for future animal studies.

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Modeling CNS microglia: the quest to identify predictive models

Cited by 31 publications

References 33 publications

LPS-induced CCL2 expression and macrophage influx into the murine central nervous system is polyamine-dependent

LPS-induced CCL2 expression and macrophage influx into the murine central nervous system is polyamine-dependent

Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system

Macrophages as Cell-Based Delivery Systems for Nanoshells in Photothermal Therapy

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