@article{lagier_manzo_carll_jaskot_slade_richards_winsett_farraj_dye_2008, title={A Hyperlipidemic Rabbit Model Provides New Insights into Pulmonary Zinc Exposure Effects on Cardiovascular Health}, volume={8}, ISSN={["1530-7905"]}, DOI={10.1007/s12012-008-9028-9}, abstractNote={This study ascertains the effects of zinc, a major component of particulate matter, on pulmonary and systemic endpoints using hyperlipidemic rabbits to model diet-induced human atherosclerosis. New Zealand White rabbits were fed a normal or cholesterol-enriched diet and then were intratracheally instilled 1x/week for 4 weeks with saline or 16 microg/kg of zinc, equal parts sulfate and oxide. Physiologic responses, blood after each exposure, and terminal bronchoalveolar lavage (BAL) were assessed. Rabbits fed a cholesterol-rich diet developed hyperlipidemia and had consistently higher circulating leukocyte counts than rabbits fed normal chow. Within minutes after zinc instillation, saturation of peripheral oxygen was decreased in hyperlipidemic rabbits and heart rate was increased in hyperlipidemic rabbits with total serum cholesterol levels greater than 200 mg/dl. Total circulating leukocytes levels were increased 24 h after the first zinc instillation, but upon repeated exposures this effect was attenuated. After repeated zinc exposures, BAL fluid (BALF) N-acetylglucosaminidase activity was increased regardless of hyperlipidemic state. Hyperlipidemic rabbits had an increase in BALF-oxidized glutathione and a decrease in serum nitrite. The study elucidates mechanisms by which the zinc metal component of PM drives cardiovascular health effects, as well as the possible susceptibility induced by hyperlipidemia. Furthermore, the study exemplifies the benefits of monitoring circulatory physiology during exposure as well as after exposure.}, number={4}, journal={CARDIOVASCULAR TOXICOLOGY}, author={LaGier, Adriana J. and Manzo, Nick D. and Carll, Alex P. and Jaskot, Richard H. and Slade, Ralph and Richards, Judy H. and Winsett, Darrell W. and Farraj, Aimen K. and Dye, Janice A.}, year={2008}, month={Dec}, pages={195–206} }
 @article{jiang_dreher_dye_li_richards_martin_adler_2000, title={Residual oil fly ash induces cytotoxicity and mucin secretion by guinea pig tracheal epithelial cells via an oxidant-mediated mechanism}, volume={163}, ISSN={["0041-008X"]}, DOI={10.1006/taap.1999.8886}, abstractNote={Inhalation of ambient air particulate matter (PM) is associated with pulmonary injury and inflammation. Using primary cultures of guinea pig tracheal epithelial (GPTE) cells as an in vitro model of airway epithelium, we examined effects of exposure to suspensions of six different emission and ambient air PM samples: residual oil fly ash (ROFA) from an electrical power plant; fly ash from a domestic oil burning furnace (DOFA); ambient air dust from St. Louis (STL), Ottawa (OT), and Washington, DC (WDC); and volcanic ash from the eruption of Mount Saint Helens (MSH) in 1980. Effects of these particulates on cell viability (assessed via LDH assay), secretion of mucin (measured by a monoclonal antibody-based ELISA), and steady-state mRNA levels of the mucin gene MUC2 were determined. ROFA was the most toxic of the dusts tested, as it significantly increased LDH release following a 24-h incubation with 50 microg/cm(2) ROFA. ROFA also enhanced MUC2 mRNA after 4-h exposure, and mucin secretion after 8 h. ROFA-induced mucin secretion and cytotoxicity were attenuated by the oxidant scavenger, dimethylthiourea (DMTU). ROFA exposure also depleted cells of glutathione (GSH). Relatedly, depletion of intracellular GSH by treatment of the cells with buthionine sulfoxamine (BSO) also provoked mucin secretion, as well as enhancing the secretory effect of ROFA when the two agents were added together. L-NMA, the nitric oxide synthase (NOS) inhibitor, did not affect ROFA-induced mucin secretion. Of the soluble transition metals in ROFA (nickel, iron, vanadium), only vanadium individually, or combinations of the metals containing vanadium, provoked secretion. The results suggest ROFA enhances mucin secretion and generates toxicity in vitro to airway epithelium via a mechanism(s) involving generation of oxidant stress, perhaps related to depletion of cellular antioxidant capacity. Deleterious effects of inhalation of ROFA in the respiratory tract in vivo may relate to these cellular responses. Vanadium, a component of ROFA, may be important in generating these reactions.}, number={3}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Jiang, NF and Dreher, KL and Dye, JA and Li, YH and Richards, JH and Martin, LD and Adler, KB}, year={2000}, month={Mar}, pages={221–230} }
 @article{dye_adler_richards_dreher_1999, title={Role of soluble metals in oil fly ash-induced airway epithelial injury and cytokine gene expression}, volume={277}, ISSN={["1040-0605"]}, DOI={10.1152/ajplung.1999.277.3.l498}, abstractNote={Particulate matter (PM) metal content and bioavailability have been hypothesized to play a role in the health effects epidemiologically associated with PM exposure, in particular that associated with emission source PM. Using rat tracheal epithelial cells in primary culture, the present study compared and contrasted the acute airway epithelial effects of an emission source particle, residual oil fly ash (ROFA), with that of its principal constitutive transition metals, namely iron, nickel, and vanadium. Over a 24-h period, exposure to ROFA, vanadium, or nickel plus vanadium, but not to iron or nickel, resulted in increased epithelial permeability, decreased cellular glutathione, cell detachment, and lytic cell injury. Treatment of vanadium-exposed cells with buthionine sulfoximine further increased cytotoxicity. Conversely, treatment with the radical scavenger dimethylthiourea inhibited the effects in a dose-dependent manner. RT-PCR analysis of RNA isolated from ROFA-exposed rat tracheal epithelial cells demonstrated significant macrophage inflammatory protein-2 and interleukin-6 gene expression as early as 6 h after exposure, whereas gene expression of inducible nitric oxide synthase was maximally increased 24 h postexposure. Again, vanadium (not nickel) appeared to be mediating the effects of ROFA on gene expression. Treatment with dimethylthiourea inhibited both ROFA- and vanadium-induced gene expression in a dose-dependent manner. Corresponding effects were observed in interleukin-6 and macrophage inflammatory protein-2 synthesis. In summary, generation of an oxidative stress was critical to induction of the ROFA- or vanadium-induced effects on airway epithelial gene expression, cytokine production, and cytotoxicity.}, number={3}, journal={AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY}, author={Dye, JA and Adler, KB and Richards, JH and Dreher, KL}, year={1999}, month={Sep}, pages={L498–L510} }
 @article{adler_jiang_dye_dreher_1998, title={Exposure of differentiated rodent airway epithelial cells in vitro to particles of residual fly ash (ROFA) induces cytotoxicity and generation of reactive oxygen species.}, volume={10}, journal={Proceedings of the 10th International Colloquium on Lung Fibrosis}, author={Adler, K. B. and Jiang, N. F. and Dye, J. A. and Dreher, K. L.}, year={1998}, pages={26} }
 @article{adler_jiang_dye_dreher_1998, title={Particles of Residual Oil Fly Ash (ROFA) induce toxicity and mucin hypersecretion in rodent airway epithelial cells in vitro via an oxidant-mediated mechanism.}, volume={95}, DOI={10.1016/s0378-4274(98)80888-6}, journal={Toxicology Letters}, author={Adler, K. B. and Jiang, N. F. and Dye, J. A. and Dreher, K. L.}, year={1998}, pages={224} }
 @article{dye_adler_rochelle_dreher_1998, title={Vanadium content and related oxidative stress appear to determine airway epithelial cell responses to emission source particulate matter.}, volume={12}, journal={FASEB Journal}, author={Dye, J. A. and Adler, K. B. and Rochelle, L. G. and Dreher, K. L.}, year={1998}, pages={A337} }
 @article{dye_adler_richards_dreher_1997, title={Airway epithelial cell responses to fly ash (ROFA) particles: contribution of soluble transition metals.}, volume={155}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Dye, J. A. and Adler, K. B. and Richards, J. H. and Dreher, K. L.}, year={1997}, pages={A197} }
 @article{dye_adler_richards_dreher_1996, title={Injury of rat tracheal epithelial cultures by exposure to residual oil fly ash (ROFA) involves generation of the hydroxyl radical.}, volume={153}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Dye, J. A. and Adler, K. B. and Richards, J. R. and Dreher, K. L.}, year={1996}, pages={A542} }
 @article{adler_krunkosky_fischer_rochelle_martin_dreher_jiang_dye_1996, title={Role or reactive oxygen and nitrogen species in the response of airway epithelium to particulates.}, volume={6}, journal={Proceedings of the 6th International Meeting of the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles.}, author={Adler, K. B. and Krunkosky, T. M. and Fischer, B. M. and Rochelle, L. G. and Martin, L. D. and Dreher, K. L. and Jiang, N. and Dye, J.}, year={1996}, pages={139} }
 @article{dye_adler_1994, title={Effects of cigarette smoke on epithelial cells of the respiratory tract.}, volume={49}, DOI={10.1136/thx.49.8.825}, abstractNote={Chronic inhalation of cigarette smoke is associated with mucus hypersecretion, mucus pooling, pulmonary connective tissue damage, and chronic airflow obstruction. Cigarette smoke has therefore been causally linked to the development of chronic obstructive pulmonary disease (either chronic bronchitis or emphysema),' increased airway responsiveness,2 exacerbations of asthma,3 impaired pulmonary immune function,4 and increased pulmonary infections.5 Cigarette smoke has also been established as an important risk factor for lung,6 laryngeal,7 and nasal neoplasia.5 Pathogenetic mechanisms related to smoke-induced respiratory perturbations, however, are not fully understood. One cell type in the lung that may play a major part in the pathogenesis of cigarette smoke-induced lesions is the airway epithelial cell. These cells line the lumen of the airways, and thus are in a unique position to interact directly with inhaled cigarette smoke. Most research involving cigarette smoke and airway epithelial cells has focused on the "target" cell responses of these cells in relation to their relatively simple roles in barrier and mucociliary clearance functions. Depending in part on the chronicity of exposure, certain functions may be altered for example, ciliary beating, mucus secretion. It has recently become apparent, however, that airway epithelial cells may also act as "effector" cells, playing pivotal roles in regulation of airway reflexes, immunological and inflammatory responses, and maintenance of bronchodilation. As part of their overall response to chronic insult these cells are capable of producing and/or releasing a number of inflammatory mediators, or undergoing alterations in expression of cell adhesion molecules processes that may initiate or perpetuate airway inflammation.9 To date the influence of cigarette smoke on effector functions of epithelial cells has yet to be investigated in detail. Much of the information presented herein is based on acute in vitro cigarette smoke exposures of epithelial cell cultures or airway explants, and on relatively acute human or laboratory animal exposures. Thus, non-neoplastic and non-emphysematous end points of respiratory disease have been emphasised. Nevertheless, early events in the response to cigarette smoke or its components may be critical, and certainly an understanding of these events may help to elucidate the pathogenetic mechanisms of many chronic respiratory diseases. Components of cigarette smoke Chemical analytical studies have identified over 3800 compounds in tobacco smoke.'" Mainstream cigarette smoke is composed of a complex mixture of gases and condensed tar particles. In experimental studies cigarette smoke is often separated into two phases by a glass fibre filter that retains nearly all particulate matter greater than 01 ptm in diameter. The retained particulate matter is commonly referred to as the "tar" phase, while the material passing through the filter is referred to as the "gas" phase. Known toxins and carcinogens have been identified in both the gaseous and particulate phases." Sidestream smoke (smoke emitted from the burning tip of the cigarette) is the major constituent of environmental tobacco smoke. The chemical composition and gas-toparticle associations of environmental tobacco smoke may be different from that of mainstream smoke, owing to prolonged time and cooling in the air.'2 Sidestream cigarette smoke emissions contain carbon monoxide, ammonia, formaldehyde, benzene, nicotine, acrolein, various gases and particles, and an assortment of potentially genotoxic and/or carcinogenic organic compounds.'3 Increased pulmonary particulate burden due to cigarette smoke may also play a part in respiratory disease.'4 Recent epidemiological findings have indicated adverse effects of particulate air pollutants at concentrations below currently permissible levels.'5 Respirable suspended particles in indoor air in homes may increase from approximately 30 jtg/ m3 to greater than 60 jg/M3 due to accumulation of environmental tobacco smoke.'6 The reported effects of "cigarette smoke" may include that of mainstream smoke, variably aged environmental tobacco smoke/sidestream and exhaled smoke, gaseous phase components only, particulate phase components only, or individual chemical compounds such as acrolein,'7 acetaldehyde,'5 or formaldehyde.'9 Some studies have used aqueous extracts of cigarette smoke obtained by bubbling the smoke through a buffer, with or without filtering to remove suspended particulates,20 while other researchers have focused on free radical production arising from chemical reactions within the cigarette smoke.2' Overall, owing to the variability in experimental methodologies (including the type of "cigarette smoke") used, interstudy comparisons may be difficult to interpret. It is well to keep this in mind when reading this review. Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA J A Dye K B Adler}, journal={404nOtfound}, author={Dye, J. A. and Adler, K. B.}, year={1994}, pages={825–834} }