Effects of Iron Status on Transpulmonary Transport and Tissue Distribution of Mn and Fe

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Abstract
Manganese transport into the blood can result from inhaling metal-containing particles. Intestinal manganese and iron absorption is mediated by divalent metal transporter 1 (DMT1) and is upregulated in iron deficiency. Since iron status alters absorption of Fe and Mn in the gut, we tested the hypothesis that iron status may alter pulmonary transport of these metals. DMT1 expression in the lungs was evaluated to explore its role in metal transport. The pharmacokinetics of intratracheally instilled 54Mn or 59Fe in repeatedly bled or iron oxide-exposed rats were compared with controls. Iron oxide exposure caused a reduction in pulmonary transport of 54Mn and 59Fe, and decreased uptake in other major organs. Low iron status from repeated bleeding also reduced pulmonary transport of iron but not of manganese. However, uptake of manganese in the brain and of iron in the spleen increased in bled rats. DMT1 transcripts were detected in airway epithelium, alveolar macrophages, and bronchial-associated lymphoid tissue in all rats. Focal increases were seen in particle-containing macrophages and adjacent epithelial cells, but no change was observed in bled rats. Although lung DMT1 expression did not correlate with iron status, differences in pharmacokinetics of instilled metals suggest that their potential toxicity can be modified by iron status.