Comparison of polarization properties of human adult microglia and blood‐derived macrophages

Durafourt, Bryce A.; Moore, Craig S.; Zammit, Domenick; Johnson, Trina; Zaguia, Fatma; Guiot, Marie‐Christine; Bar‐Or, Amit; Antel, Jack P.

doi:10.1002/glia.22298

Cited by 424 publications

(399 citation statements)

References 42 publications

(53 reference statements)

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“…For example, some in vitro studies have suggested that human microglia develop polarization responses that are distinct from macrophages and show a tendency to maintain M2 properties under stimulation. 42 Validation of these observations in vivo in TBI is, however, difficult at the present time because of the paucity of specific markers to distinguish microglia from macrophages.…”

Section: Discussionmentioning

confidence: 99%

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

Wang

Zhang

et al. 2013

J Cereb Blood Flow Metab

408

331

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Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilament SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation-induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment.

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Section: Discussionmentioning

confidence: 99%

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

Wang

Zhang

et al. 2013

J Cereb Blood Flow Metab

408

331

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“…In addition, M1 and M2 macrophages express different repertoires of phagocytic receptors and may show differential efficiency of endocytosis and phagocytosis (18,19). It appears that the effect of macrophage polarization on phagocytosis is target dependent: M1 macrophages show enhanced phagocytosis of S. aureus (20), while M2 macrophages are more phagocytic toward myelin (21), apoptotic cells, and latex beads (22). The development of T cell-based immune responses requires days to weeks and would not be immediately provoked by exposure to particles.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Jones¹,

Roberts²,

Robbins³

et al. 2013

J. Clin. Invest.

177

164

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Extended circulation of nanoparticles in blood is essential for most clinical applications. Nanoparticles are rapidly cleared by cells of the mononuclear phagocyte system (MPS). Approaches such as grafting polyethylene glycol onto particles (PEGylation) extend circulation times; however, these particles are still cleared, and the processes involved in this clearance remain poorly understood. Here, we present an intravital microscopybased assay for the quantification of nanoparticle clearance, allowing us to determine the effect of mouse strain and immune system function on particle clearance. We demonstrate that mouse strains that are prone to Th1 immune responses clear nanoparticles at a slower rate than Th2-prone mice. Using depletion strategies, we show that both granulocytes and macrophages participate in the enhanced clearance observed in Th2-prone mice. Macrophages isolated from Th1 strains took up fewer particles in vitro than macrophages from Th2 strains. Treating macrophages from Th1 strains with cytokines to differentiate them into M2 macrophages increased the amount of particle uptake. Conversely, treating macrophages from Th2 strains with cytokines to differentiate them into M1 macrophages decreased their particle uptake. Moreover, these results were confirmed in human monocyte-derived macrophages, suggesting that global immune regulation has a significant impact on nanoparticle clearance in humans. IntroductionThe potential clinical applications of nanoparticles and nanoformulations have been investigated for more than 30 years. Nanoparticle approaches have the potential to revolutionize drug delivery by allowing for the encapsulation of drugs with poor solubility or stability in a stable carrier particle. In addition, targeting nanoparticles to specific pathological sites may allow an increased effective dose of drug at the needed site, while decreasing systemic drug exposure, and therefore side effects. However, to date, only 2 nanoformulations for cancer treatment have been approved for clinical use (liposomal doxorubicin [Doxil] and protein-bound paclitaxel [Abraxane]) (1-3). One major obstacle for the use of nanoparticles in vivo is rapid clearance by the cells of the reticuloendothelial system (RES)/mononuclear phagocyte system (MPS) (4-7). In addition to rapid clearance, variable activity of the MPS among patients leads to widely variable pharmacokinetics of nanoformulations in the clinic, reducing the efficacy of both approved and future experimental nanoformulations (8).

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“…The M2 anti-inflammatory phenotype has been related with the production of anti-inflammatory cytokines and is associated with regeneration properties and wound healing Zhang 2015, Ransohoff andPerry 2009). Furthermore, the M2 phenotype resolution and regenerative properties have been related with inducing OPCs differentiation, remyelination and promoting myelin clearance (Durafourt et al 2012, Kotter et al 2006, Miron et al 2013, Wang et al 2015, Yu et al 2015.…”

Section: Discussionmentioning

confidence: 99%

“…These cells are readily polarized to a M1 phenotype by incubation 71 with LPS (10-100 ng/ml)+IFNγ (20 ng/ml) and to a M2 phenotype by incubation with IL-4 (10-20 ng/ml) (Classen et al 2009). These conditions were used as controls of phenotypic changes for 24h the morphology of cells changed from a more rounded/amoeboid type to an elongated shape similar to that acquired when BMDM are treated with IL-4 (Durafourt et al 2012, McWhorter et al 2013, Vereyken et al 2011). …”

Section: Treatments That Increase Cgmp Induce Phenotype Changes In Bmdmmentioning

confidence: 99%

“…Myelin clearance correlates with increased remyelination and differentiation of OPCs (Kotter et al 2006, Miron andFranklin 2014). Furthermore, recent reports indicate that M2 cells have higher myelin phagocytic activity than M1 cells (Durafourt et al 2012) and that M2 cell polarization is essential for efficient remyelination (Miron et al 2013). To investigate if sildenafil treatment affects myelin debris phagocytosis in EAE mice we performed Oil-red O (ORO) staining in longitudinal SC sections.…”

Section: Sildenafil Increases Myelin Phagocytosis In Microglia/macropmentioning

confidence: 99%

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Mechanisms Involved in the Remyelinating Effect of Sildenafil

Díaz-Lucena

Gutièrrez‐Mecinas

Moreno

et al. 2017

J Neuroimmune Pharmacol

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ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials dʼinvestigació i docència en els termes establerts a lʼart. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix lʼautorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No sʼautoritza la seva reproducció o altres formes dʼexplotació efectuades amb finalitats de lucre ni la seva comunicació pública des dʼun lloc aliè al servei TDX. Tampoc sʼautoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.ADVERTENCIA. El acceso a los contenidos de esta tesis doctoral y su utilización debe respetar los derechos de la persona autora. Puede ser utilizada para consulta o estudio personal, así como en actividades o materiales de investigación y docencia en los términos establecidos en el art. 32 del Texto Refundido de la Ley de Propiedad Intelectual (RDL 1/1996). Para otros usos se requiere la autorización previa y expresa de la persona autora. En cualquier caso, en la utilización de sus contenidos se deberá indicar de forma clara el nombre y apellidos de la persona autora y el título de la tesis doctoral. No se autoriza su reproducción u otras formas de explotación efectuadas con fines lucrativos ni su comunicación pública desde un sitio ajeno al servicio TDR. Tampoco se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR (framing). Esta reserva de derechos afecta tanto al contenido de la tesis como a sus resúmenes e índices.WARNING.

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Comparison of polarization properties of human adult microglia and blood‐derived macrophages

Cited by 424 publications

References 42 publications

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

Nanoparticle clearance is governed by Th1/Th2 immunity and strain background

Mechanisms Involved in the Remyelinating Effect of Sildenafil

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