An &lt;em&gt;In vitro&lt;/em&gt; Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization

Erbel, Christian; Rupp, Gregor; Helmes, Christian M.; Tyka, Mirjam; Linden, Fabian; Doesch, Andreas O.; Katus, Hugo A.; Gleissner, Christian A.

doi:10.3791/50332

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…Slight increases in pro-inflammatory cytokines (but no overt toxicity) were observed at ≥5 µg/cm 2 in murine macrophages (cf Table 6) . Apart from the fact that the relevance of this in vitro murine model is questionable with regard to humans, see, for example, (Erbel et al 2013; Mestas and Hughes 2004), the exposure levels were unrealistically high. Even under the assumption of direct contact with the intestinal epithelium (which in fact is protected by a mucous layer and is composed of different cell types) and an intake of up to 1500 mg/day (EFSA 2009), the amount of E 551 in the intestinal lumen would not reach an in vitro effective dose level (taking into account that the mean total mucosal surface of the digestive tract interior averages 32 m 2 (Helander and Fandriks 2014), up to 4.6 µg/cm 2 could theoretically be estimated for the intestinal lumen).…”

Section: Discussionmentioning

confidence: 98%

The safety of nanostructured synthetic amorphous silica (SAS) as a food additive (E 551)

Fruijtier-Pölloth¹

2016

Arch Toxicol

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Key messages Particle sizes of E 551 products are in the micrometre range. The typical external diameters of the constituent particles (aggregates) are greater than 100 nm. E 551 does not break down under acidic conditions such as in the stomach, but may release dissolved silica in environments with higher pH such as the intestinal tract. E 551 is one of the toxicologically most intensively studied substances and has not shown any relevant systemic or local toxicity after oral exposure. AbstractSynthetic amorphous silica (SAS) meeting the specifications for use as a food additive (E 551) is and has always been produced by the same two production methods: the thermal and the wet processes, resulting in E 551 products consisting of particles typically in the micrometre size range. The constituent particles (aggregates) are typically larger than 100 nm and do not contain discernible primary particles. Particle sizes above 100 nm are necessary for E 551 to fulfil its technical function as spacer between food particles, thus avoiding the caking of food particles. Based on an in-depth review of the available toxicological information and intake data, it is concluded that the SAS products specified for use as food additive E 551 do not cause adverse effects in oral repeated-dose studies including doses that exceed current OECD guideline recommendations. In particular, there is no evidence for liver toxicity after oral intake. No adverse effects have been found in oral fertility and developmental toxicity studies, nor are there any indications from in vivo studies for an immunotoxic or neurotoxic effect. SAS is neither mutagenic nor genotoxic in vivo. In intact cells, a direct interaction of unlabelled and unmodified SAS with DNA was never found. Differences in the magnitude of biological responses between pyrogenic and precipitated silica described in some in vitro studies with murine macrophages at exaggerated exposure levels seem to be related to interactions with cell culture proteins and cell membranes. The in vivo studies do not indicate that there is a toxicologically relevant difference between SAS products after oral exposure. It is noted that any silicon dioxide product not meeting established specifications, and/or produced to provide new functionality in food, requires its own specific safety and risk assessment.

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Section: Discussionmentioning

confidence: 98%

The safety of nanostructured synthetic amorphous silica (SAS) as a food additive (E 551)

Fruijtier-Pölloth¹

2016

Arch Toxicol

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“…Primary human macrophages were collected from 30 mL of citrate-treated blood samples and prepared according to standard techniques (13). Briefly, blood was separated on a Ficoll-Paque Plus gradient by centrifugation at 750 × g for 20 minutes without braking.…”

Section: Methodsmentioning

confidence: 99%

Heme Oxygenase-1 Regulates Inflammation and Mycobacterial Survival in Human Macrophages during Mycobacterium tuberculosis Infection

Scharn

Collins

Nair

et al. 2016

The Journal of Immunology

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Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that Mtb infection in mice induces expression of the carbon monoxide (CO) producing enzyme heme oxygenase (HO1) and that CO is sensed by Mtb to initiate a dormancy program. Further, mice deficient in HO1 succumb to Mtb infection more readily than wild type mice. While mouse macrophages control intracellular Mtb infection through several mechanisms such as nitric oxide synthase, the respiratory burst, acidification and autophagy, how human macrophages control Mtb infection remains less well understood. Here we show that Mtb induces and colocalizes with HO1 in both mouse and human tuberculosis lesions in vivo, and that Mtb induces and colocalizes with HO1 during primary human macrophage infection in vitro. Surprisingly, we find that chemical inhibition of HO1 both reduces inflammatory cytokine production by human macrophages and restricts intracellular growth of mycobacteria. Thus, induction of HO1 by Mtb infection may be a mycobacterial virulence mechanism to enhance inflammation and bacterial growth.

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“…M1 MΦs are the classical activated MΦs, which produce pro-inflammatory cytokines such as TNF-Φ and IL-12 and clear pathogens but also cause tissue damage. In contrast, M2 MΦs are alternatively activated, which generate anti-inflammatory mediators such as IL-10, suppress facilitate wound healing and inflammation (Erbel et al, 2013 ). It was proved that some medicine and compounds could induce MΦ polarization to M1-like MΦs or M2-like MΦs (Gharib et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Biochanin a Enhances the Defense Against Salmonella enterica Infection Through AMPK/ULK1/mTOR-Mediated Autophagy and Extracellular Traps and Reversing SPI-1-Dependent Macrophage (MΦ) M2 Polarization

Zhao

Tang

Guo

et al. 2018

Front. Cell. Infect. Microbiol.

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A novel treatment regimen for bacterial infections is the pharmacological enhancement of the host's immune defenses. We demonstrated that biochanin A (BCA), an isoflavone constituent in some plants, could enhance both intra- and extracellular bactericidal activity of host cells. First, BCA could induce a complete autophagic response in nonphagocytic cells (HeLa) or macrophages (MΦ) via the AMPK/ULK1/mTOR pathway and Beclin-1-dependent manner, and BCA enhanced the killing of invading Salmonella by autophagy through reinforcing ubiquitinated adapter protein (LRSAM1, NDP52 and p62)-mediated recognition of intracellular bacteria and through the formation of autophagolysosomes. Second, we demonstrated that BCA could enhance the release of MΦ extracellular traps (METs) to remove extracellular Salmonella also via the AMPK/ULK1/mTOR pathway, not through reactive oxygen species (ROS) pathway. Furtherly, in a Salmonella-infected mouse model, BCA treatment increased intra- and extracellular bactericidal activity through the strengthening autophagy and MET production, respectively, in peritoneal MΦ, liver and spleen tissue. Additionally, our findings showed that BCA downregulated SPI-1 (Salmonella pathogenicity island 1) expression during Salmonella infection in vitro and in vivo to reverse the MΦ M2 polarization, which was different from the MΦ M1 phenotype caused by most of bacteria infection. Together, these findings suggest that BCA has an immunomodulatory effect on Salmonella-infected host cells and enhances their bactericidal activity in vitro and in vivo through autophagy, extracellular traps and regulation of MΦ polarization.

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An <em>In vitro</em> Model to Study Heterogeneity of Human Macrophage Differentiation and Polarization

Cited by 10 publications

References 20 publications

The safety of nanostructured synthetic amorphous silica (SAS) as a food additive (E 551)

The safety of nanostructured synthetic amorphous silica (SAS) as a food additive (E 551)

Heme Oxygenase-1 Regulates Inflammation and Mycobacterial Survival in Human Macrophages during Mycobacterium tuberculosis Infection

Biochanin a Enhances the Defense Against Salmonella enterica Infection Through AMPK/ULK1/mTOR-Mediated Autophagy and Extracellular Traps and Reversing SPI-1-Dependent Macrophage (MΦ) M2 Polarization

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