HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figures and Tables All Versions of this Article: 295/1/L79    most recent 00048.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Tamagawa, E. Articles by van Eeden, S. F. PubMed PubMed Citation Articles by Tamagawa, E. Articles by van Eeden, S. F.

Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction

¹Division of Respiratory Medicine, University of British Columbia and James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Vancouver, British Columbia, Canada; ²Division of Respiratory Disease, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan; and ³Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada

Submitted 1 February 2007 ; accepted in final form 2 May 2008

Epidemiologic and animal studies have shown that exposure to particulate matter air pollution (PM) is a risk factor for the development of atherosclerosis. Whether PM-induced lung and systemic inflammation is involved in this process is not clear. We hypothesized that 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. New Zealand White rabbits were exposed for 5 days (acute, total dose 8 mg) and 4 wk (chronic, total dose 16 mg) to either PM smaller than 10 µm (PM₁₀) or saline intratracheally. Lung inflammation was quantified by morphometry; systemic inflammation was assessed by white blood cell and platelet counts and serum interleukin (IL)-6, nitric oxide, and endothelin levels. Endothelial dysfunction was assessed by vascular response to acetylcholine (ACh) and sodium nitroprusside (SNP). PM₁₀ exposure increased lung macrophages (P < 0.02), macrophages containing particles (P < 0.001), and activated macrophages (P < 0.006). PM₁₀ increased serum IL-6 levels in the first 2 wk of exposure (P < 0.05) but not in weeks 3 or 4. PM₁₀ exposure reduced ACh-related relaxation of the carotid artery with both 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). Exposure to PM₁₀ caused lung and systemic inflammation that were both associated with vascular endothelial dysfunction. This suggests that PM-induced lung and systemic inflammatory responses contribute to the adverse vascular events associated with exposure to air pollution.

air pollution; alveolar macrophage; systemic inflammation; interleukin-6