Respiratory tract responses to dust: Relationships between dust burden, lung injury, alveolar macrophage fibronectin release, and the development of pulmonary fibrosis

Driscoll, Kevin E.; Maurer, James K.; Lindenschmidt, Robert C.; Romberger, Debra J.; Rennard, Stephen I.; Crosby, Leslie

doi:10.1016/0041-008x(90)90109-8

Cited by 83 publications

(34 citation statements)

References 29 publications

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“…However, recent investigations on the basis of both experimental studies on rats and epidemiologic surveys revealed the development of inflammation, pulmonary damage, fibrosis, and lung tumors after exposure to ultrafine TiO 2 (UF-TiO 2 ) (4-9). Dimensions of the TiO 2 particles are pivotal, as demonstrated by the fact that UFTiO 2 causes more pronounced toxicity compared with fine TiO 2 particles (10)(11)(12).…”

mentioning

confidence: 99%

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Rahman

Lohani

Dopp

et al. 2002

Environ Health Perspect

355

218

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Inhaled ultrafine titanium dioxide (UF-TiO2) particles cause pronounced pulmonary inflammation, in contrast to fine TiO2. Previous studies provide evidence for the production of reactive oxygen species by alveolar macrophages, after overloading with UF-TiO2 particles and cytotoxicity of UF-TiO2 in rat lung alveolar macrophages. UF-TiO2 also causes pulmonary fibrosis and lung tumors in rats. UF-TiO2 particles are photogenotoxic, but in general, information on the genotoxicity of UF-TiO2 is still limited. We studied the potential of UF-TiO2 (particle size less than or equal to 20 nm) and fine TiO2 (particle size > 200 nm) to induce chromosomal changes, which can be monitored by the formation of micronuclei (MN) in Syrian hamster embryo (SHE) cells. We also analyzed UF-TiO2-treated cells for apoptosis induction. The MN assay revealed a significant increase in MN induction (p less than or equal to 0.05) in SHE cells after treatment with UF-TiO2 (1.0 micro g/cm2) for 12 hr (mean, 24.5 MN/1,000 cells), 24 hr (mean, 31.13 MN/1,000 cells), 48 hr (mean, 30.8 MN/1,000 cells), 66 hr (mean, 31.2 MN/1,000 cells), and 72 hr (mean, 31.3 MN/1,000 cells). Bisbenzimide staining of the fixed cells revealed typical apoptotic structures (apoptotic bodies), and the apoptosis-specific "DNA ladder pattern" resulting from internucleosomal cleavage was identified by gel electrophoresis. Furthermore, transmission electron microscopy of the exposed cells revealed the typical chromatin compaction of apoptosis.

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mentioning

confidence: 99%

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Rahman

Lohani

Dopp

et al. 2002

Environ Health Perspect

355

218

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“…Protein content was assayed using a commercially available kit (Wako Pure Chemical Industries, Osaka, Japan). Fibronectin content was determined by enzyme-linked immunosorbent assay as previously described (6 …”

Section: Pleurl Lavage Fluidmentioning

confidence: 99%

Comparison of pleural responses of rats and hamsters to subchronic inhalation of refractory ceramic fibers.

Everitt

Gelzleichter

Bermudez

et al. 1997

Environ Health Perspect

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In the present subchronic study, we compared pleural inflammation, visceral pleural collagen deposition, and visceral and parietal pleural mesothelial cell proliferation in rats and hamsters identically exposed to a kaolin-based refractory ceramic fiber, (RCF)-1 by nose-only inhalation exposure, and correlated the results to translocation of fibers to the pleural cavity. Fischer 344 rats and Syrian golden hamsters were exposed to 650 fibers/cc of RCF-1, for 4 hr/day, 5 days/week for 12 weeks. Following 4 and 12 weeks of exposure, and after a 12-week recovery period, pleural lavage fluid was analyzed for cytologic and biochemical evidence of inflammation. Visceral and parietal pleural mesothelial cell proliferation was assessed by immunocytochemical detection of bromodeoxyuridine incorporation. Pleural collagen was quantitated using morphometric analysis of lung sections stained with Sirius Red. Fiber-exposed rats and hamsters had qualitatively similar pleural inflammation at each time point. Mesothelial cell proliferation was more pronounced in hamsters than in rats at each time point and at each site. In both species, the mesothelial cell labeling index was highest in the parietal pleural mesothelial cells lining the surface of the diaphragm at each time point. Hamsters but not rats had significantly elevated collagen in the visceral pleura at the 12-week postexposure time point. Fibers were found in the pleural cavities of both species at each time point. These fibers were generally short and thin. These results suggest that mesothelial cell proliferation and fibroproliferative changes in the pleura of rodents following short-term inhalation exposure are associated with fiber translocation to the pleura and may be predictive of chronic pleural disease outcomes following long-term exposure.

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“…Lung fibrosis and obstructive diseases 15,28,95,96,122,194,274 , inflammatory responses 189,212,232,275,276 and cardiovascular 45,73,117,277,278 implications have all been associated with PM10 and PM2.5 inhalation, although prediction of long term health outcomes remains unclear by any other metric than size, though various factors have been proposed as indicators of fibrotic potential 57,73,196,279 . Inorganic transition metal such as iron may have unique modes of action and catalytic potentials 132 .…”

Section: Discussionmentioning

confidence: 99%

“…Mineral dusts generated by mining can also cause systemic toxicity through chemical speciation and free radical generation 117 , provoke hyperplasia and cancer 28,100,118 and elevate cardiovascular risks, likely through inducing systemic inflammation 73 , as well as cause pneumoconiosis with potentially distinctive characteristics on X-ray 100 . Clinical pathologies of excess mineral dust inhalation often take years to manifest, but usually present as a fibrotic pneumoconiosis of variable granulation, nodulation and opacity with possible complications depending on exposure, as distinguishable on x-ray radiographs (see Table 4) 95,100,119 .…”

Section: Pulmonary Pathologies Of Mining Dust Inhalationmentioning

confidence: 99%

“…Both PM toxicity and concentration were independently found to exacerbate PAM death, reducing clearance rate and therefore increasing PM retention in the interstitial spaces of the lung. Persistent pro-inflammatory and pro-fibrotic immunological signalling was theorised to then initiate the fibrosing aspects of lung tissue damage and remodelling 13,[23][24][25][26][27][28][29][30][31][32] . Under this paradigm, experiments were designed to show how otherwise inert PM could exhaust the PAM pool increasing insoluble alveolar PM load and halflife in acute exposures 30,33,34 , demonstrating the importance of volumetric load, in addition particle number alone.…”

Section: Introductionmentioning

confidence: 99%

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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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Respiratory tract responses to dust: Relationships between dust burden, lung injury, alveolar macrophage fibronectin release, and the development of pulmonary fibrosis

Cited by 83 publications

References 29 publications

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.

Comparison of pleural responses of rats and hamsters to subchronic inhalation of refractory ceramic fibers.

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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