Academic journal article Environmental Health Perspectives

Global Gene Expression Profiling in Whole-Blood Samples from Individuals Exposed to Metal Fumes

Academic journal article Environmental Health Perspectives

Global Gene Expression Profiling in Whole-Blood Samples from Individuals Exposed to Metal Fumes

Article excerpt

Accumulating evidence demonstrates that particulate air pollutants can cause both pulmonary and airway inflammation. However, few data show that particulates can induce systemic inflammatory responses. We conducted an exploratory study using microarray techniques to analyze wholeblood total RNA in boilermakers before and after occupational exposure to metal fumes. A self-controlled study design was used to overcome the problems of larger between-individual variation interferences with observations of relatively smaller changes caused by environmental exposure. Moreover, we incorporated the dichotomous data of absolute gene expression status in the microarray analyses. Compared with nonexposed controls, we observed that genes with altered expression in response to particulate exposure were clustered in biologic processes related to inflammatory response, oxidative stress, intracellular signal transduction, cell cycle, and programmed cell death. In particular, the preinflammatory cytokine interleukin 8 and one of its receptors, chemokine receptor 4, seemed to play important roles in early-stage response to heavy metal exposure and were down-regulated. Furthermore, most observed expression variations were from nonsmoking exposed individuals, suggesting that smoking profoundly affects whole-blood expression profiles. Our study is the first to demonstrate that with a paired sampling study design of pre- and postexposed individuals, small changes in gene expression profiling can be measured in whole-blood total RNA from a population-based study. This technique can be applied to evaluate the host response to other forms of environmental exposures. Key words: functional pathway, gene expression profiling, inflammation, occupational particulate exposure, whole-blood total RNA. doi:10.1289/txg.7273 available via http://dx.doi.org/ [Online 22 November 2004]

**********

Exposure to ambient particulate air pollution is associated with increases in morbidity and mortality from respiratory and cardiovascular diseases (Godleski et al. 2000). The welding process generates high levels of metal fume containing respirable particles. Epidemiologic studies have shown that acute exposure to welding fume is associated with metal-fume fever (Mueller and Seger 1985) and increased reversible respiratory symptoms (El-Zein et al. 2003a; Wolf et al. 1997). There was an increased prevalence of inflammatory lung diseases, such as asthma and chronic bronchitis, among welders (El-Zein et al. 2003b). Additionally, accumulating epidemiologic evidence in the last decade has pointed to the associations of particulate exposure with adverse cardiovascular effects (Dockery et al. 1993; Mann et al. 2002; Peters et al. 2000, 2001a; Pope et al. 2002). Limited evidence indicates that welding-fume exposure also may be associated with increased cardiovascular events (Sjogren et al. 2002).

It has been proposed that inhaled particulates from air pollution may cause systemic alterations by the release of inflammatory cytokines subsequent to pulmonary inflammation, which plays an important role in the pathogenesis of atherosclerosis and coronary diseases. Indeed, elevated ambient particulate levels have been shown to be associated with increased levels of inflammatory markers, such as white blood cell (WBC) counts (Schwartz 2001), C-reactive protein (CRP; Peters et al. 2001b; Seaton et al. 1999), and fibrinogen (Pekkanen et al. 2000; Schwartz 2001) in both cross-sectional and longitudinal epidemiologic observations. In the experimental setting, animal studies have revealed that concentrated ambient particulate exposures increase the total WBC counts and the differential count of circulating neutrophils (Clarke et al. 2000; Gordon et al. 1998) in both healthy animals and those with pulmonary hypertension. Intratracheal instillation of residual oil fly ash (ROFA) can induce a significant elevation of plasma fibrinogen in cardiopulmonary-compromised rats (Gardner et al. …

Search by... Author
Show... All Results Primary Sources Peer-reviewed

Oops!

An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.