- Full (HTML) - Full (PDF) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

John A. Lewis,¹ K. Murali Krishna Rao,² Vince Castranova,² Val Vallyathan,² William E. Dennis,¹ and Paul L. Knechtges¹

¹U.S. Army Center for Environmental Health Research, Fort Detrick, Maryland, USA; ²Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia, USA

Abstract
Background: Inhalation of diesel exhaust particles (DEPs) is characterized by lung injury and inflammation, with significant increases in the numbers of polymorphonuclear leukocytes and alveolar macrophages. This influx of cellular infiltrates is associated with the activation of multiple genes, including cytokines and chemokines, and the production of reactive oxygen species.

Objective: The pathogenesis of the lung injury is not fully understood, but alterations in the presence or abundance of a number of proteins in the lung have been observed. Our objective in this study was to further characterize these changes and to ask whether additional changes could be discerned using modern proteomic techniques.

Methods: The present study investigates global alterations in the proteome of bronchoalveolar lavage fluid taken from rats 1, 7, or 30 days after exposure to 5, 35, or 50 mg/kg of animal weight of DEPs.

Results: Analysis by surface-enhanced laser desorption/ionization–time of flight mass spectrometry identified two distinct peaks that appeared as an acute response postexposure at all doses in all animals. We identified these two peaks, with mass to charge ratios (m/z) of 9,100 and 10,100, as anaphylatoxin C3a and calgranulin A by additional mass spectral investigation using liquid chromatography coupled to mass spectrometry.

Conclusions: With this approach, we found a number of inflammatory response proteins that may be associated with the early phases of inflammation in response to DEP exposure. Further studies are warranted to determine whether serum levels of these proteins could be markers of diesel exhaust exposure in workers.

Key words: calprotectin, diesel, inflammation, macrophage, mass spectrometry, proteomics, SELDI. Environ Health Perspect 115:756–763 (2007) . doi:10.1289/ehp.9745 available via http://dx.doi.org/ [Online 5 February 2007]

Address correspondence to J.A. Lewis, U.S. Army Center for Environmental Health Research, 568 Doughten Dr., Ft. Detrick, MD 21740 USA. Telephone: (301) 619-7209. Fax: (301) 619-7606. E-mail: john.a.lewis1@us.army.mil

We thank D. Jackson for critical review and suggestions for the manuscript.

The research described here was sponsored by the Department of the Army, U.S. Army Medical Research and Materiel Command, Military Operational Medicine Research Program, and NIOSH.

Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army or NIOSH. Citations of commercial organizations or trade names in this report do not constitute an official DA or NIOSH endorsement or approval of the products or services of these organizations.

The authors declare they have no competing financial interests.

Received 21 September 2006 ; accepted 5 February 2007.