title: 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.
authors: Department of Environmental Health, National Public Health Institute, Kuopio, Finland. Mikko.Happo@ktl.fi
authors: M S
authors: MS
authors: Happo
authors: R O
authors: RO
authors: Salonen
authors: A I
authors: AI
authors: Hälinen
authors: P I
authors: PI
authors: Jalava
authors: A S
authors: AS
authors: Pennanen
authors: V M
authors: VM
authors: Kosma
authors: M
authors: M
authors: Sillanpää
authors: R
authors: R
authors: Hillamo
authors: B
authors: B
authors: Brunekreef
authors: K
authors: K
authors: Katsouyanni
authors: J
authors: J
authors: Sunyer
authors: M-R
authors: MR
authors: Hirvonen
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D011506:Proteins / Q000032:analysis; D013997:Time Factors
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D052638:Particulate Matter; D011506:Proteins