Determinants of the Proinflammatory Action of Ambient Particulate Matter in Immortalized Murine Macrophages

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【标题】Determinants of the Proinflammatory Action of Ambient Particulate Matter in Immortalized Murine Macrophages

【作者】 Cecilia Guastadisegni  Frank J. Kelly  Flemming R Cassee  Miriam E. Gerlofs-Nijland  Nicole A.H. Janssen  Roberta Pozzi  Bert A Brunekreef  Thomas Sandstr?m  Ian S. Mudway 

【关键词】Metal Inflammatory Potential FINE PM Samples Endotoxin 

【摘要】BACKGROUND Proximity to traffic-related pollution has been associated with poor respiratory health in adults and children. OBJECTIVES We wished to test the hypothesis that particulate matter (PM) from high-traffic sites would display an enhanced capacity to elicit inflammation. METHODS We examined the inflammatory potential of coarse [2.5-10 μm in aerodynamic diameter (PM(2.5-10))] and fine [0.1-2.5 μm in aerodynamic diameter (PM(0.1-2.5))] PM collected from nine sites throughout Europe with contrasting traffic contributions. We incubated murine monocytic-macrophagic RAW264.7 cells with PM samples from these sites (20 or 60 μg/cm2) and quantified their capacity to stimulate the release of arachidonic acid (AA) or the production of interleukin-6 and tumor necrosis factor-α (TNFα) as measures of their inflammatory potential. Responses were then related to PM composition: metals; hydrocarbons; anions/cations; and endotoxin content. RESULTS Inflammatory responses to ambient PM varied markedly on an equal mass basis; with PM(2.5-10) displaying the largest signals and contrasts among sites. Notably; we found no evidence of enhanced inflammatory potential at high-traffic sites and observed some of the largest responses at sites distant from traffic. Correlation analyses indicated that much of the sample-to-sample contrast in the proinflammatory response was related to the content of endotoxin and transition metals (especially iron and copper) in PM(2.5-10). Use of the metal chelator diethylene triamine pentaacetic acid inhibited AA release; whereas recombinant endotoxin-neutralizing protein partially inhibited TNFα production; demonstrating that different PM components triggered inflammatory responses through separate pathways. CONCLUSIONS We found no evidence that PM collected from sites in close proximity to traffic sources displayed enhanced proinflammatory activity in RAW264.7 cells.

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