title: Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.
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.
authors.affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown 26505, WV, USA. efi4@cdc.gov.
authors.forename: Aaron
authors.initials: A
authors.lastname: Erdely
authors.forename: James M
authors.initials: JM
authors.lastname: Antonini
authors.forename: Shih-Houng
authors.initials: SH
authors.lastname: Young
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.forename: Ja K
authors.initials: JK
authors.lastname: Gu
authors.forename: Tracy
authors.initials: T
authors.lastname: Hulderman
authors.forename: Rebecca
authors.initials: R
authors.lastname: Salmen
authors.forename: Terence
authors.initials: T
authors.lastname: Meighan
authors.forename: Jenny R
authors.initials: JR
authors.lastname: Roberts
authors.forename: Patti C
authors.initials: PC
authors.lastname: Zeidler-Erdely
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D016867:Immunocompromised Host; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013193:Stainless Steel / Q000633:toxicity*; D013997:Time Factors; D014158:Transcription, Genetic; D014896:Welding
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D052638:Particulate Matter; D012333:RNA, Messenger; D013193:Stainless Steel