Inflammation and tissue damage in mouse lung by single and repeated dosing of urban air coarse and fine particles collected from six European cities

Abstract

The authors have previously demonstrated heterogeneities in the inflammatory activities of urban air fine (PM_2.5–0.2) and coarse (PM_10–2.5) particulate samples collected from six European cities with contrasting air pollution situations. The same samples (10 mg/kg) were intratracheally instilled to healthy C57BL/6J mice either once or repeatedly on days 1, 3, and 6 of the study week. The lungs were lavaged 24 h after the single dose or after the last repeated dosing. In both size ranges, repeated dosing of particles increased the total cell number in bronchoalveolar lavage fluid (BALF) more than the respective single dose, whereas cytokine concentrations were lower after repeated dosing. The lactate dehydrogenase (LDH) responses increased up to 2-fold after repeated dosing of PM_2.5–0.2 samples and up to 6-fold after repeated dosing of PM_10–2.5 samples. PM_10–2.5 samples evoked a more extensive interstitial inflammation in the mouse lungs. The constituents with major contributions to the inflammatory responses were oxidized organic compounds and transition metals in PM_2.5–0.2 samples, Cu and soil minerals in PM_10–2.5 samples, and Zn in both size ranges. In contrast, poor biomass and coal combustion were associated with elevated levels of polycyclic aromatic hydrocarbons (PAHs) and a consistent inhibitory effect on the inflammatory activity of PM_2.5–0.2 samples. In conclusion, repeated intratracheal instillation of both fine and coarse particulate samples evoked enhanced pulmonary inflammation and cytotoxicity compared to single-dose administration. The sources and constituents of urban air particles responsible for these effects appear to be similar to those encountered in the authors’ previous single-dose study.

Keywords:

• Inflammation
• tissue damage
• particulate matter
• sources
• repeated dosing

Acknowledgements

The authors are grateful to all the PAMCHAR teams in the respective cities conducting the field work and collaborating in the project. We also highly appreciate the assistance provided by MSc Anna Frey, PhD Sanna Saarikoski and MSc Ulla Makkonen (Finnish Meteorological Institute); and MSc Erik Sandell and Ms Sirpa Himberg (Technical Research Centre of Finland, VTT Processes, Espoo, FI), Ms Heli Martikainen, Ms Arja Rönkkö, Ms Reetta Tiihonen and BSc Janne Korkalainen (National Public Health Institute, Kuopio, FI), Ms Päivi Heikura and Ms Liisa Kauppinen (Kuopio University Hospital, Finland), and technical consultation by Mr John Boere (National Institute of Public Health and the Environment, Bilthoven, NL) and the statistical assistance by MSc Pekka Tiittanen (National Public Health Institute, Kuopio, FI).

Declaration of interest

The authors are grateful for funding by the EC-FP5 Quality of Life and Management of Living Resources Programme (Contract QLK4-CT-2001-00423), the Academy of Finland (contracts 201701 and 53307), the Finnish Funding Agency for Technology and Innovation (Tekes, contract 40715/01) and The Ministry of Education (The Graduate School on Environmental Health, SYTYKE). The PAMCHAR project belongs to the COST Action 633 on Particulate matter: properties related to health effects (http://cost633.dmu.dk). The authors alone are responsible for the content and writing of the paper.