Submitted on February 1, 2007
Accepted on May 2, 2008
Particulate Matter Exposure Induces Persistent Lung Inflammation and Endothelial Dysfunction
Eiji Tamagawa1, Ni Bai1, Kiyoshi Morimoto1, Claire Gray1, Tammy Mui1, Kazuhiro Yatera2, Xuekui Zhang1, Li Xing1, Yuexin Li1, Ismail Laher3, Don D Sin1, S.F.Paul Man1, and Stephan F. van Eeden4*
1 Division of Respiratory Medicine, The University of British Columbia and The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research(St. Paul's Hosp), Vancouver, Canada
2 Division of Respiratory Disease, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan
3 Department of Anesthesiology, Pharmacology & Therapeutics, The University of British Columbia, Vancouver, Vancouver, Canada
4 Pathology, The University of British Columbia and The James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research(St. Paul's Hosp), Vancouver, Canada
* To whom correspondence should be addressed. E-mail: svaneeden{at}mrl.ubc.ca.
Epidemiologic and animal studies have shown that exposure to particulate matter air pollution (PM) is a risk factor for the development of atherosclerosis. Whether the PM-induced lung and systemic inflammation is involved in this process, is not clear. [Hypothesis] PM exposure causes lung and systemic inflammation, which in turn leads to vascular endothelial dysfunction, a key step in the initiation and progression of atherosclerosis. [Method] New Zealand White rabbits were exposed for 5 days (acute, total dose 8mg) and 4 weeks (chronic, total dose 16mg) to either PM10 or saline intratracheally. Lung inflammation was quantified using morphometry, systemic inflammation was assessed by white blood cell and platelet counts, serum interleukin (IL)-6 and Nitric Oxide and Endothelin levels. Endothelial dysfunction was assessed by vascular response to Acetylcholine (ACh) and sodium nitroprusside (SNP). [Results] PM10 exposure increased lung macrophages (p<0.02), macrophages containing particles (p<0.001) and activated macrophages (p<0.006). In the first 2 weeks of exposure, PM10 increased serum IL-6 levels (p<0.05) but not in week 3 or 4. PM10 exposure reduced ACh-related relaxation of the carotid artery with both the acute and chronic exposure with no effect on SNP-induced vasodilatation. Serum IL-6 levels correlated with macrophages containing particles (p=0.043), and ACh- induced vasodilatation (p=0.014 at week 1, p=0.021 at week 2). [Conclusion] Exposure to PM10 caused lung and systemic inflammation that were both associated with vascular endothelial dysfunction. This suggests that the PM-induced lung and systemic inflammatory responses contribute to the adverse vascular events associated with exposure to air pollution.
