Limits...
Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.

Erdely A, Antonini JM, Young SH, Kashon ML, Gu JK, Hulderman T, Salmen R, Meighan T, Roberts JR, Zeidler-Erdely PC - Part Fibre Toxicol (2014)

Bottom Line: In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown 26505, WV, USA. efi4@cdc.gov.

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.

Show MeSH

Related in: MedlinePlus

Experimental design of rats intratracheally instilled with either phosphate buffered saline (PBS) or manual metal arc stainless steel (MMA-SS) welding fume.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4151022&req=5

Figure 1: Experimental design of rats intratracheally instilled with either phosphate buffered saline (PBS) or manual metal arc stainless steel (MMA-SS) welding fume.

Mentions: The complete experimental design is shown in Figure 1. Rats (n = 7 per group) were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a MMA-SS weld. Rats were sacrificed 4 and 24 h post-exposure by exsanguination under isoflurane anesthesia and whole blood was collected with heparin as the anticoagulant. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation utilizing TruCulture technology from Myriad/RBM as described in detail in the Materials and Methods section.


Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats.

Erdely A, Antonini JM, Young SH, Kashon ML, Gu JK, Hulderman T, Salmen R, Meighan T, Roberts JR, Zeidler-Erdely PC - Part Fibre Toxicol (2014)

Experimental design of rats intratracheally instilled with either phosphate buffered saline (PBS) or manual metal arc stainless steel (MMA-SS) welding fume.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4151022&req=5

Figure 1: Experimental design of rats intratracheally instilled with either phosphate buffered saline (PBS) or manual metal arc stainless steel (MMA-SS) welding fume.
Mentions: The complete experimental design is shown in Figure 1. Rats (n = 7 per group) were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a MMA-SS weld. Rats were sacrificed 4 and 24 h post-exposure by exsanguination under isoflurane anesthesia and whole blood was collected with heparin as the anticoagulant. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation utilizing TruCulture technology from Myriad/RBM as described in detail in the Materials and Methods section.

Bottom Line: In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown 26505, WV, USA. efi4@cdc.gov.

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.

Show MeSH
Related in: MedlinePlus