Regular articleEffect of polystyrene particles on lung microvascular permeability in isolated perfused rabbit lungs: role of size and surface properties
Introduction
Ambient particulate matter with diameter less than 10 μm (PM10) has been associated with increased mortality and morbidity linked to respiratory and cardiovascular causes in several epidemiological studies Dockery et al 1993, Ostro et al 1993, Pope et al 2002. These effects are especially prominent in susceptible parts of the population with preexisting cardiovascular diseases or inflammatory lung diseases such as chronic obstructive pulmonary disease (COPD) or asthma Peters et al 1997a, Sunyer and Basagana 2001. The mechanisms responsible for these adverse health effects are not yet completely understood—especially regarding cardiovascular effects—and further studies are needed to determine the underlying biological mechanisms. The release of inflammatory mediators such as cytokines from the lung tissue is the main hypothesis (Seaton et al., 1995), but recent evidence suggests that myocardial and blood dysfunctions induced by inhaled PM10 could be due to passage of some particles from the lung into the systemic circulation Nemmar et al 2001, Nemmar et al 2002a, Takenaka et al 2001. Both mechanisms could interact since the passage of particles or particle-loaded macrophages into the interstitium or blood could be increased due to a modification of epithelial and endothelial permeability induced by inflammatory mediators (Donaldson et al., 2001b). Thus, the effects of particles on pulmonary microvascular permeability can be considered as a relevant question.
PM10 consists of a very wide range of solid or liquid particles that are small enough to remain suspended in air for long periods. Physical properties such as size, shape, density, or chemical composition of particles are very heterogeneous. Therefore, the comparison of the dose–response effect of the different types of particles cannot be readily done. In most experimental and epidemiological studies, the most common way to express the exposure dose is to combine the level of ambient particles suspended in the atmosphere, generally expressed as the weight of particles per cubic meter (μg/m3), with time of exposure. The gravimetric dose is also used in experimental studies when the particles are instilled in the respiratory tract and is expressed as the weight of administered particles to animals. However, this approach does not take into account the particle number. The latter parameter plays an important role, especially with regards to ultrafine particles (UFP), with a diameter below 100 nm (Donaldson et al., 2001a). Although they constitute only 1 to 8% of the mass of particulate matter, they are numerous in ambient air Oberdorster et al 2000, Peters et al 1997b. In these conditions, lung cells exposed to UFP will likely respond differently compared to an equivalent gravimetric dose of larger particles such as coarse particles. Although some studies demonstrate the effects of size, number, and total surface area of particles Lison et al 1997, Hetland et al 2001, the influence of these parameters is not well known, especially for the smallest particles. In addition, the chemical surface of particles is an important factor modulating the effects of particles (Hetland et al., 2000). In the present study we attempted to assess these factors with polystyrene particles of various sizes and surface charge in an isolated perfused lung model.
The first objective was to assess using an isolated perfused lung preparation the pulmonary microvascular changes induced by intratracheally instilled carboxylate-modified particles in relation to the mass, number, and total surface area of instilled particles. Second, we compared the effects induced by carboxylate-modified versus amine-modified particles.
Section snippets
Animals
Twenty-eight New Zealand rabbits aged from 10 to 14 weeks (2.79 ± 0.5 kg) were used. Animals were housed on a fully slatted plastic floor during 10 to 15 days before the experiment. Light and ventilation were standardised. The ethics committee of the University of Liège approved the experimental protocol.
Ex vivo model of rabbit isolated ventilated and perfused lungs: general procedure
After the animals had been deeply anesthetised by xylazine (8 mg/kg im Rompun; Bayer, Brussels, Belgium) and ketamine (50 mg/kg im Imalgene 1000; Mérial, Brussels, Belgium), the trachea of each
Influence of size and quantity of polystyrene particles on capillary filtration coefficient (Kf,c)
Table 2 shows the dose- and time-dependent influence of carboxylate-modified particles of different diameters on the microvascular permeability. Administration of these particles induced a significant time-dependent increase in the Kf,c values in all treated groups but not in controls. Moreover, significant or borderline significant (p < 0.1) differences between controls and treated groups are also observed after 30 min. Values found in groups II and III are significantly lower than those of
Discussion
This study was initiated to investigate the role of basic physical characteristics of intratracheally instilled fine and ultrafine microspheres on the pulmonary microvascular permeability in isolated perfused rabbit lung. The rationale for choosing commercial microspheres was that this enabled a good characterization in terms of mass, diameter, number, individual surface area, and total surface area. Moreover, these particles avoid the complications of potential components of ambient particles
Acknowledgements
This research was funded by the Fonds National de la Recherche Scientifique (FNRS) and the University of Liège (Belgium). Dr Julien Hamoir and Dr Alain Vanderplasschen are Research Fellow and Senior Research Associate of the FNRS, respectively. Purchase of the confocal microscope was supported by the following grants: FRFC 2.4532.98 from the FNRS, FNRS LOTTO 9.4592.97 from the Belgian National lottery, and ARC 98/03-220 from the French Community of Belgium.
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