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Systemic immune cell response in rats after pulmonary exposure to manganese-containing particles collected from
James M Antonini1, Patti C Zeidler-Erdely, Shih-Houng Young
1Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. jga6@cdc.gov
Abstract:
Welding fume inhalation affects the immune system of exposed workers. Manganese (Mn) in welding fume may induce immunosuppressive effects. The goal was to determine if Mn in welding fume alters immunity by reducing the number of circulating total leukocytes and specific leukocyte sub-populations. Sprague-Dawley rats were treated by intratracheal instillation (ITI) with either a single dose (2.00 mg/rat) or repeated doses (0.125 or 2.00 mg/rat for 7 weeks) with welding fumes that contained different levels of Mn. Additional rats were treated by ITI once a week for 7 weeks with the two doses of manganese chloride (MnCl₂). Bronchoalveolar lavage was performed to assess lung inflammation. Also, whole blood was recovered, and the number of circulating total leukocytes, as well as specific lymphocyte subsets, was determined by flow cytometry. The welding fume highest in Mn content significantly increased lung inflammation, injury, and production of inflammatory cytokines and chemokines compared to all other treatment groups. In addition, the same group expressed significant decreases in the number of circulating CD4⁺ and CD8⁺ T-lymphocytes after a single exposure, and significant reductions in the number of circulating total lymphocytes, primarily CD4⁺ and CD8⁺ T-lymphocytes, after repeated exposures (compared to control values). Repeated MnCl₂ exposure led to a trend of a reduction (but not statistically significant) in circulating total lymphocytes, attributable to the changes in the CD4⁺ T-lymphocyte population levels. The welding fume with the lower concentration of Mn had no significant effect on the numbers of blood lymphocytes and lymphocyte subsets compared to control values. Evidence from this study indicates that pulmonary exposure to certain welding fumes cause decrements in systemic immune cell populations, specifically circulating T-lymphocytes, and these alterations in immune cell number are not dependent exclusively on Mn, but likely a combination of other metals present in welding fume.
Insights
Welding fumes containing high manganese levels significantly reduced circulating T-lymphocytes in rats, indicating immunosuppression. These immune changes are linked to welding fume composition beyond just manganese.
Area of Science:
- Immunotoxicology
- Occupational Health
- Environmental Exposure
Background:
- Welding fume inhalation poses risks to worker immune systems.
- Manganese (Mn) within welding fumes is a suspected contributor to immunosuppression.
- Understanding the specific immune effects of welding fume components is crucial for worker safety.
Purpose of the Study:
- To investigate if manganese in welding fumes alters immune status.
- To assess changes in circulating leukocyte and lymphocyte subset counts.
- To differentiate the effects of manganese versus complex welding fume mixtures.
Main Methods:
- Rats received single or repeated intratracheal instillations of welding fumes with varying Mn levels or manganese chloride (MnCl₂).
- Lung inflammation was evaluated via bronchoalveolar lavage.
- Circulating leukocyte and lymphocyte subsets (CD4+, CD8+) were quantified using flow cytometry.
Main Results:
- High-Mn welding fume exposure increased lung inflammation, injury, and cytokine production.
- Significant decreases in circulating CD4+ and CD8+ T-lymphocytes were observed after single and repeated exposures to high-Mn fume.
- Repeated MnCl₂ exposure showed a non-significant trend towards reduced lymphocytes, suggesting other fume components contribute to immune effects.
Conclusions:
- Pulmonary exposure to specific welding fumes can impair systemic immune cell populations, particularly circulating T-lymphocytes.
- The observed immune alterations are likely due to a combination of metals in welding fume, not solely manganese.
- This study highlights the complex immunotoxic potential of occupational welding fume exposure.