Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory response in the mouse lung

¹ Ludwig-Maximilians-University, Institute for Epidemiology, D-85758 Neuherberg/Munich, Germany; and GSF-National Research Center for Environment and Health, Institute for Epidemiology, D-85758 Neuherberg/Munich, Germany
² GSF-National Research Center for Environment and Health, Institute for Inhalation Biology, D-85758 Neuherberg/Munich, Germany
³ Ludwig-Maximilians-University, Institute for Epidemiology, D-85758 Neuherberg/Munich, Germany
⁴ GSF-National Research Center for Environment and Health, Institute for Epidemiology, D-85758 Neuherberg/Munich, Germany

^* To whom correspondence should be addressed. E-mail: tobias.stoeger{at}gsf.de.

	Abstract

High levels of particulate matter in ambient air are associated with increased respiratory and cardiovascular health problems. It has been hypothesized that it is the ultrafine particle fraction (diameter<100 nm) which is largely responsible for these effects. To evaluate the associated mechanisms on a molecular level, we applied an expression profiling approach.

We exposed healthy mice to either ultrafine carbon particles (mass concentration: 380 µg·m^-3) or filtered air for 4 and 24 hours. Histology of the lungs did not indicate any pathomorphological changes after inhalation. Examination of the bronchoalveolar lavage fluid revealed a small increase in polymorphonuclear cell number (from 0.6% to 1%) after ultrafine particle inhalation, as compared to clean air controls, suggesting a minor inflammatory response. However, DNA microarray profile analysis revealed a clearly biphasic response to particle exposure. After 4 hours of inhalation, mainly heat shock proteins were induced, whereas after 24 hours different immunomodulatory proteins (osteopontin, galectin-3 and lipocalin-2) were upregulated in alveolar macrophages and septal cells.

These data indicate that inhalation of ultrafine carbon particles triggers a biphasic pro-inflammatory process in the lung involving the activation of macrophages and the up-regulation of immunomodulatory proteins.

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