Dose and Time Dependency of Inflammatory Responses in the Mouse Lung to Urban Air Coarse, Fine, and Ultrafine Particles From Six European Cities

Abstract

We investigated the dose and time dependency of inflammatory and cytotoxic responses to size-segregated urban air particulate samples in the mouse lung. Coarse (PM10-2.5), fine (PM2.5-0.2), and ultrafine (PM0.2) particles were collected in six European cities (Duisburg, Prague, Amsterdam, Helsinki, Barcelona, Athens) in selected seasons using a modified Harvard high-volume cascade impactor. Healthy C57Bl/6J mice were intratracheally exposed to the particulate samples in a 24-h dose-response study (1, 3, and 10 mg/kg) and in 4-, 12-, and 24-h time course studies (10 mg/kg). After the exposures, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: total cell number, cell differential, total protein, and lactate dehydrogenase (LDH) and cytokine (tumor necrosis alpha [TNF-alpha], interleukin-6 [IL-6], and keratinocyte-derived chemokine [KC]) concentrations. In general, PM10-2.5 samples had higher inflammatory activity than PM2.5-0.2 samples. PM0.2 samples showed negligible inflammatory activity. PM10-2.5 and PM2.5-0.2 samples caused large increases in BALF cytokine concentrations at 4 h, but not at 12 or 24 h, after exposure. The BALF total cell number and total protein concentrations increased significantly at 12 h for both the PM10-2.5 and PM2.5-0.2 samples, but only PM10-2.5 samples produced consistent, significant increases at 24 h after exposure. There was more heterogeneity in BALF cytokine and neutrophil cell number responses to PM2.5-0.2 samples than to PM10-2.5 samples between the sampling campaigns. Thus, particle size, sources, and atmospheric transformation processes affect the inflammatory activity and response duration of urban air particulate matter in the mouse lung.

Impact of Biomass Combustion on Urban Fine Particulate Matter in Central and Northern Europe

“…The sampling durations were 3 or 4 days in alternation with the total number of 13-15 samples collected in each city. The sampling duration was rather long due to the need to collect large amounts of particulate mass for toxicological studies Happo et al 2007). In Table 1, the sampling campaigns with some meteorological parameters (mean temperature, precipitation sum and global radiation), and background information on the major local sources of particulate emissions in the cities are summarized.…”

“…The samples of this study were collected in the multinational PAMCHAR-EU project that was launched in 2002 to provide an extensive physicochemical and toxicological characterization of sizesegregated particulate matter (Sillanpää et al 2005;Jalava et al 2007;Happo et al 2007). The field campaigns were carried out one after another corresponding to contrasting air pollution situations of public health interest in Europe.…”

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

“…This is also reflected in an in-vivo study using PM from six different European cities, where the coarse fraction was found to be consistently more inflammatory than the fine fraction, although fines caused greater neutrophil accumulation 189 .…”

“…However, differential effects between PM10 and PM2.5 do exist, and PM2.5 correlations are not universally accepted as more powerful 49,51,53,62,89,189 . This is especially evident from the pulmonary morbidity associated with increases in coarse fraction mineral PM10-2.5 during dust storms 60,61 , which have similarities to mining dusts.…”

“…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 .…”