Increased oxidative stress with reduced responsiveness of circulating leukocytes following pulmonary metal‐rich particulate matter exposure

Abstract

Pulmonary exposure to metal‐rich particulate matter (PM) generated from welding causes localized immunosuppression. The aim of this study was to evaluate the molecular changes and responsiveness of circulating leukocytes following exposure. Rats were exposed to manual metal arc stainless steel welding fume (MMAW‐SS) at 2 mg/rat by intratracheal instillation and sacrificed at 4 and 24 hr post‐exposure. Collected whole blood was then challenged with and without LPS for 24 hr. After incubation, supernatants were collected for protein analysis and the cellular fraction was collected for global gene expression changes. Also, mononuclear cells were isolated and analyzed for oxidative stress by flow cytometry and confocal microscopy. Ex vivo leukocyte stimulation with LPS showed reduced production of CCL4, CXCL2, CXCL10 and TNF‐alpha protein in MMAW‐SS treated rats. Interestingly, cellular gene expression changes from MMAW‐SS and PBS rats were similar indicating effects were not related to transcription. Since oxidative stress can affect translation, isolated mononuclear cells were tested and showed increased basal levels of oxidative stress. These results showed increased oxidative stress with a reduced responsiveness of circulating leukocytes providing mechanistic insight into epidemiological and experimental evidence illustrating immunosuppression following a metal‐rich PM exposure.