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

• Published in: Inhalation toxicology Vol. 19; no. 3; pp. 227 - 246
• Main Authors: Happo, M. S., Salonen, R. O., Hälinen, A. I., Jalava, P. I., Pennanen, A. S., Kosma, V. M., Sillanpää, M., Hillamo, R., Brunekreef, B., Katsouyanni, K., Sunyer, J., Hirvonen, M.-R.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.03.2007; Taylor & Francis
• Subjects: Air Pollutants - toxicity; Animals; Cell Count; Cell Differentiation - drug effects; Cytokines - analysis; Cytokines - biosynthesis; Dose-Response Relationship, Drug; Lung - drug effects; Lung - metabolism; Lung - pathology; Male; Mice; Mice, Inbred C57BL; Particle Size; Particulate Matter - toxicity; Proteins - analysis; Time Factors; Spain, Cataluna, Barcelona; Netherlands, Noord-Holland, Amsterdam; Finland, Etelae-Suomi, Helsinki
• ISSN: 0895-8378; 1091-7691
• DOI: 10.1080/08958370601067897

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-α], 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.