Potential of coculture in vitro models to study inflammatory and sensitizing effects of particles on the lung

Klein, Sebastian G.; Hennen, Jenny; Serchi, Tommaso; Blömeke, Brunhilde; Gutleb, Arno C.

doi:10.1016/j.tiv.2011.09.006

Cited by 73 publications

(62 citation statements)

References 227 publications

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“…Thus, it appears that GGT1 can be expressed in normal human lung; candidates are Clara cells and alveolar type II epithelium, which were previously found to express GGT in rat lung (11,12). The A549 cell line has alveolar type II-like characteristics (50). However, human PBECs, which differ from alveolar epithelium in several respects (36,50), did not express GGT1 (Fig.…”

Section: Formation Of Cyslt In Coincubations Of Pbecs With Mm6 Cellsmentioning

confidence: 74%

“…MM6 and A549 cells have been combined before in coculture models of pulmonary inflammation; e.g., when cocultures of A549 and MM6 cells were exposed to ultrafine particles, cytokine release (IL-6 and IL-8) was increased in comparison to monocultures of the respective cells [see (50) and references therein]. Also, growth of mycobacteria in MM6 cells was reduced when MM6 were in coculture with A549 cells, which was attributed to A549-derived cytokines (particularly TNF) (60).…”

Section: Formation Of Cyslt In Coincubations Of Pbecs With Mm6 Cellsmentioning

confidence: 99%

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Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

Lukić

Jie

Idborg

et al. 2016

Journal of Lipid Research

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Leukotrienes (LTs) are mediators of inflammation (1) formed by immune cells in response to pathogens or danger signals. When cells are stimulated, cytosolic phospholipase A 2  (cPLA 2 ) and 5-lipoxygenase (LO) migrate to the nuclear membrane, arachidonic acid (AA) is released from nuclear membrane phospholipids, and LTA 4 is produced (2). Efficient translocation and activation of 5-LO requires two scaffold proteins, 5-LO activating protein (FLAP) and coactosin-like protein (CLP) (3). LTA 4 is then further metabolized by cytosolic LTA 4 hydrolase to LTB 4 , or by LTC 4 synthase (LTC 4 S) to LTC 4 . LTC 4 S is primarily located at the nuclear membrane together with FLAP, and both proteins are members of the family of membrane bound proteins involved in eicosanoid and glutathione metabolism (MAPEG). LTC 4 and its metabolites, LTD 4 and LTE 4 , are jointly referred to as the cysteinyl LTs (CysLTs). CysLTs elicit edema formation, mucus secretion, and smooth muscle contraction, as well as eosinophil trafficking and tissue remodeling, and thus contribute to symptoms in several chronic inflammatory diseases, such as asthma (4). There are at least three different receptors for the CysLTs; in the lung, bronchoconstriction and other effects are mediated via CysLT1. LTD 4 has a 10-to 50-fold higher potency for activation of CysLT1 compared with LTC 4 , while LTE 4 is the least active (5, 6). Thus, metabolism of LTC 4 to LTD 4 may have a considerable impact on CysLT1-mediated effects, also depending on further conversion to LTE 4 . Abstract Leukotrienes (LTs

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Section: Formation Of Cyslt In Coincubations Of Pbecs With Mm6 Cellsmentioning

confidence: 74%

Section: Formation Of Cyslt In Coincubations Of Pbecs With Mm6 Cellsmentioning

confidence: 99%

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

Lukić

Jie

Idborg

et al. 2016

Journal of Lipid Research

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“…The human respiratory tract contains nearly 50 different cell types along its hierarchical structure (14) in distinct proximal (conducting) and distal (respiratory) zones (8). The larger proximal airways include the trachea, bronchi and bronchioles of greater than 2mm in diameter; these regions are reinforced by cartilaginous rings to prevent collapse ( Fig.…”

Section: Anatomy and Physiology Of The Airwaysmentioning

confidence: 99%

“…Common cell-based models, for example, consist of two-dimensional (2D) monolayers of a single tracheobronchial epithelial immortalised cell line cultured on a semi-permeable membrane insert at an air-liquid interface (ALI) to induce cell polarisation, differentiation and mucus production. Although such models are useful as a tool for drug transport studies (6), they fall short in toxicity studies as they lack the physiological complexity of the airways (7,8).…”

Section: Introductionmentioning

confidence: 99%

Respiratory Tissue Engineering: Current Status and Opportunities for the Future

O’Leary

Gilbert

O’Dea

et al. 2015

Tissue Engineering Part B: Reviews

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“…IL-10 expression was near that of U937. IL-10 is thought to be a respiratory sensitiser, leading to humoral immunity and allergic responses 186 .…”

Section: Oxidative Stressmentioning

confidence: 99%

In-vitro toxicology of respirable iron-rich particles relevant to mining industry: a high throughput framework for interpreting environmental particulate matter toxicity

Prakash¹

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This project investigated the cytotoxicity profiles and toxicological properties of inhalable iron-rich particles generated by mining activity. National Environment Protection Measure (NEPM) ambient air quality regulations specifically regulate sub-10 µm (PM10) and sub-2.5 µm (PM2.5) diameter particle fractions corresponding to thoracic and respirable lung penetration, respectively. However, atmospheric concentrations of fugitive iron-rich particulates in iron ore mining and processing associated settlements raised concerns that NEPM limits may inadequately address the specific toxicological profile of iron-rich PM10 and potentially adsorbed organics in these regions. To address this, comparative cytotoxicity experiments were carried out in-vitro using a variety of particulate standards, featuring other frequently studied metal-oxides, to help bridge in-vivo and epidemiological knowledge in the literature with in-vitro toxicological results. This also required the development of a novel framework to interpret physical and physiological characteristics of coarse, poorly soluble metal-oxide particles by conducting a critical systematic literature review.Analysis by the ChemCentre, WA was taken into account with relation to potentially absorbed organics and the influence of Polycyclic Aromatic Hydrocarbons (PAHs) investigated.The protocols developed by this project are applicable to high-throughput assessment of particulate matter generated by mining activity, having defined methodology to rapidly acquire sufficient quantities of PM10 for assays which can be multiplexed and the effects of particulate interference on assays minimised. This includes the integration of non-destructive sterilisation techniques, physical characterising by particle-sizing, particle solubility analysis and observation of particle morphology by electron microscopy and elemental analysis. Epithelial (A549), fibroblast (LL24) and monocyte differentiated macrophage (U937) cell lines were tested to build a picture of particulate effects on the major lung cell types in the lung parenchyma; the alveolar epithelium, connective tissue and immune system.The effect of lung fluid surfactants on cytotoxicity was determined, and advanced tissue culture methods were trialled to improve the differentiation between particles provided by the endpoints.ii The ore samples from the Mining Area C (MAC), Yandi and Newman Hub mines in the Pilbara region were found to have an effect comparable to the cytotoxicity of micron-size iron oxide standards and selected standards of titanium dioxide, silicon dioxide and carbon black, whereas copper oxide was found to have some ten-fold greater cytotoxicity across the cell lines. However cytotoxicity as a principle differentiator of toxicity was found to be insufficient in differentiating the physiological response to iron-rich PM10 and insoluble metal-oxide standards. At high concentrations the dose-response relationship plateaued at a maximum value for iron-oxide standards and iron ore samples in the A549 and LL2...

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Potential of coculture in vitro models to study inflammatory and sensitizing effects of particles on the lung

Cited by 73 publications

References 227 publications

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4

Respiratory Tissue Engineering: Current Status and Opportunities for the Future

In-vitro toxicology of respirable iron-rich particles relevant to mining industry: a high throughput framework for interpreting environmental particulate matter toxicity

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