John A. Lewis US Army Center for Environ. Health Res. Office: 301-619-7209 FAX: E-mail: john.lewis@det.amedd.army.mil Job Title: Research Biologist Ph.D. in Biology from the University of Pittsburgh

Speaker: John A. Lewis, US Army Center for Environmental Health Research (USACEHR), Fort Detrick, Frederick, MD 21701

Topic: Proteomic Analysis of Bronchoalveolar Lavage Fluid: Effect of Acute Exposure to Diesel Exhaust Particles in Rats

Place: Building 549, Auditorium, Frederick National Laboratory for Cancer Research, Frederick, MD

Time: Tuesday, October 10, 2006, at 2:00 PM

Abstract: Inhalation of diesel exhaust particles (DEP) 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. 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. The present study investigates global alterations in the abundance of proteins in bronchoalveolar lavage fluid taken from rats 1, 7 or 30 days after exposure to 5, 35 or 50 mg / kg of animal weight of DEP. Analysis by surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF) identified two distinct peaks that appeared as an acute response post-exposure at all doses in all animals. These two peaks, with mass to charge ratios (m/z) of 9,100 and 10,100, were identified as anaphylatoxin C3a and calgranulin A by additional mass spectral investigation using liquid chromatography coupled to mass spectrometry (LC/MS). With this approach, we found a number of other inflammatory response proteins which 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.