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Published ahead of print on December 13, 2007, doi:10.1165/rcmb.2007-0204OC

Am. J. Respir. Cell Mol. Biol., Volume 38, Number 5, May 2008, 532-540

A more recent version of this article appeared on May 1, 2008
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Submitted on June 6, 2007
Revised on December 10, 2007

Combustion-Derived Hydrocarbons Localize to Lipid Droplets in Respiratory Cells

Gleeson Murphy, Jr.1, Rodney L Rouse1, William W Polk1, William G Henk1, Steven A Barker1, Marc J Boudreaux2, Z. Elizabeth Floyd3, and Arthur L Penn1*

1 Comparative Biomedical Sciences, Louisiana State University, School of Veterinary Medicine, Baton Rouge, LA, USA, 2 Division of Biotechnology and Molecular Medicine (BioMMED), Louisiana State University, School of Veterinary Medicine, Baton Rouge, LA, USA, 3 Louisiana State University, Pennington Biomedical Research Center, Baton Rouge, LA, USA

* To whom correspondence should be addressed. E-mail: apenn{at}vetmed.lsu.edu.

Combustion-generated radicals interact forming polynuclear aromatic hydrocarbons (PAHs), including carcinogens. PAHs aggregate into 20-50 nm particles, which extend into branched-chain structures (soots). Many PAHs, including those in soots, fluoresce upon excitation. We have reported that butadiene soot (BDS), generated during combustion of the high volume petrochemical, 1,3-butadiene, serves as a reproducible example of combustion-derived fine and ultrafine particles, with the potential for acute or delayed health effects. Human bronchoepithelial cells (BEAS-2B) display time- and concentration-dependent responses to BDS exposure, culminating in concentration of fluorescent PAHs within discrete cytoplasmic bodies. Here we identify the cytoplasmic compartment(s) in which combustion-derived PAHs concentrate and assess the metabolic responses associated with this compartmentalization. BDS-associated fluorescence co-localized with a red fluorescent cholesterol analog and a transfected plasmid coding for a fluorescent lipid droplet surface protein within BEAS-2B cells. After BDS exposure, murine alveolar macrophages (MH-S) and adipocytes (3T3-L1) also develop fluorescence. These findings, especially within adipocytes, support the accumulation of PAHs within lipid droplets. Microarray data revealed up-regulation of aryl hydrocarbon receptor (AhR)-induced Phase I biotransformation enzymes and nuclear erythroid-2 related factor 2 (NRF2)-mediated oxidative stress responses in BEAS-2B cells. Quantitative RT-PCR results confirmed a time-dependent up-regulation of Phase I biotransformation enzymes (CYP1A1, CYP1B1 and ALDH3A1) in BDS-exposed BEAS-2B and MH-S cells. Thus, respiratory cell lipid droplets concentrate PAHs delivered by combustion-derived ultrafine particles. These PAHs, including several found in BDS and in cigarette smoke, activate xenobiotic metabolism pathways and thereby potentiate their toxicity.






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Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2007 American Thoracic Society.