Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of met
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RESEARCH
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Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats Aaron Erdely1,3*, James M Antonini1, Shih-Houng Young2, Michael L Kashon1, Ja K Gu1, Tracy Hulderman1, Rebecca Salmen1, Terence Meighan1, Jenny R Roberts1 and Patti C Zeidler-Erdely1
Abstract Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. Keywords: Microarray, Welding, Immunosuppression, Cardiovascular disease, Chromium, Whole blood cell gene expression
Introduction Pulmonary exposures to particulates, recognized for local effects in the lung, are now widely studied for their effects related to cardiovascular, immunological, and neurological dysfunction. Occupational exposure to welding fume is an exposure that is known to cause effects on extrapulmonary systems in all three categories. Welding joins two metals at high temperatures and generates an aerosol of * Correspondence: [email protected] 1 Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA 3 NIOSH/HELD/PPRB, 1095 Willowdale Rd, MS-2015, Morgantown, WV 26505-2888, USA Full list of author information is available at the end of the article
gases and a fume that contains a metal-rich particulate fraction. Millions of workers weld as a part of their job duties with more than 430,000 full-time welders in the United States [1]. Data sugges
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