Inflammatory Effect of Intratracheal Instillation of Ultrafine Particles in the Rabbit: Role of C-fiber and Mast Cells

Nemmar, Abderrahim; Delaunois, Annie; Nemery, Benoît; Dessy-Doize, C.; Beckers, Jean‐François; Sulon, Joseph; Gustin, Pascal

doi:10.1006/taap.1999.8762

Cited by 45 publications

(26 citation statements)

References 34 publications

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“…Peroxidative damage to the endothelial membrane provides the initial stimulus for platelet adhesion and thrombus formation. 23,24 The time point investigated here (1 hour) is shorter than the 6 hours 9 or 20 to 24 hours 25,26 in other studies of the acute effects of particles, but it may well be particularly relevant for understanding pollutant-promoted myocardial infarction. 6 The choice of 1 hour was based on our recent work that showed that UFPs diffuse rapidly (within minutes) from the lungs into the systemic circulation in hamster 14 and in humans.…”

Section: Discussionmentioning

confidence: 98%

Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis

et al. 2003

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Background-Pollution by particulates has consistently been associated with increased cardiovascular morbidity and mortality, but a plausible biological basis for this association is lacking. Methods and Results-Diesel exhaust particles (DEPs) were instilled into the trachea of hamsters, and blood platelet activation, experimental thrombosis, and lung inflammation were studied. Doses of 5 to 500 g of DEPs per animal induced neutrophil influx into the bronchoalveolar lavage fluid with elevation of protein and histamine but without lactate dehydrogenase release. The same doses enhanced experimental arterial and venous platelet rich-thrombus formation in vivo. Blood samples taken from hamsters 30 and 60 minutes after instillation of 50 g of DEPs yielded accelerated aperture closure (ie, platelet activation) ex vivo, when analyzed in the Platelet Function Analyser (PFA-100).The direct addition of as little as 0.5 g/mL DEPs to untreated hamster blood significantly shortened closure time in vitro. Conclusions-The intratracheal instillation of DEPs leads to lung inflammation as well as a rapid activation of circulating blood platelets. The kinetics of platelet activation are consistent with the reported clinical occurrence of thrombotic complications after exposure to pollutants. Our findings, therefore, provide a plausible explanation for the increase in cardiovascular morbidity and mortality accompanying urban air pollution.

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Section: Discussionmentioning

confidence: 98%

Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis

et al. 2003

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“…As expected, histamine caused a marked increase in microvascular permeability (and vascular constriction) and this led to a clear fluorescent signal in BAL. This approach is relevant because histamine concentrations have been shown to increase following particle exposure of human basophils in vitro (Devouassoux et al, 2002;Kepley et al, 2003), after instillation of particles in isolated tracheally perfused rabbit lung ex vivo (Nemmar et al, 1999), as well as in hamsters in vivo (Nemmar et al, 2003a(Nemmar et al, , 2003c and in healthy human volunteers (Salvi et al, 1999). We hypothesize that, in these experimental conditions, migration of particles occurred by passive mechanisms through intercellular spaces (Conhaim et al, 1988) and we suggest that particles cannot cross the capillaryalveolar barrier unless microvascular permeability is altered and in the presence of a positive driving force provided by fluid filtration.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of particle translocation across the alveolo-capillary barrier in isolated perfused rabbit lung model

et al. 2005

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“…In lung histopathology, PM plays a crucial role, because there is a signi cant transport of ultra ne PM from the epithelium to the interstitium, and to the endothelial and intravascular compartments in these exposed dogs. Ultra ne particles are associated with stronger in ammatory responses, prolonging of their lung retention, induction of procollagen expression, and increases in airway brosis (6,44,87). Ultra ne particles less than 0.1 um possess unique physicochemical features (64), are produced by the burning of fossil fuels or photochemical reactions, can easily penetrate into deep lung regions, and are deposited in the lung by diffusion; deposition spreads over large areas of the lung.…”

Section: Discussionmentioning

confidence: 99%

Air Pollution and Brain Damage

et al. 2002

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Exposure to complex mixtures of air pollutants produces in ammation in the upper and lower respiratory tract. Because the nasal cavity is a common portal of entry, respiratory and olfactory epithelia are vulnerable targets for toxicological damage. This study has evaluated, by light and electron microscopy and immunohistochemica l expression of nuclear factor-kappa beta (NF-j B) and inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF-j B and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks; subsequen t damage included alterations of the blood-brain barrier (BBB), degenerating cortical neurons, apoptotic glial white matter cells, deposition of apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and pericytes, nonneuritic plaques, and neuro brillary tangles. Persistent pulmonary in ammation and deteriorating olfactory and respiratory barriers may play a role in the neuropatholog y observed in the brains of these highly exposed canines. Neurodegenerativ e disorders such as Alzheimer's may begin early in life with air pollutants playing a crucial role.

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Inflammatory Effect of Intratracheal Instillation of Ultrafine Particles in the Rabbit: Role of C-fiber and Mast Cells

Cited by 45 publications

References 34 publications

Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis

Diesel Exhaust Particles in Lung Acutely Enhance Experimental Peripheral Thrombosis

Evaluation of particle translocation across the alveolo-capillary barrier in isolated perfused rabbit lung model

Air Pollution and Brain Damage

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