Effects of iron status on transpulmonary transport and tissue distribution of Mn and Fe

Area of Science:

• Environmental toxicology
• Pulmonary medicine
• Metal transport

Background:

• Inhaled metal particles can lead to manganese transport into the bloodstream.
• Intestinal absorption of manganese and iron is regulated by divalent metal transporter 1 (DMT1), with increased expression in iron deficiency.
• Iron status is known to affect gut absorption of iron and manganese.

Purpose of the Study:

• To investigate if iron status affects pulmonary transport of metals.
• To evaluate the role of DMT1 expression in the lungs for metal transport.

Main Methods:

• Rats were subjected to repeated bleeding (to induce iron deficiency) or iron oxide exposure.
• The pharmacokinetics of intratracheally instilled radioactive manganese (54Mn) and iron (59Fe) were compared between exposed and control groups.
• DMT1 gene expression in lung tissues was analyzed.

Main Results:

• Iron oxide exposure reduced pulmonary transport and organ uptake of both 54Mn and 59Fe.
• Repeated bleeding decreased pulmonary iron transport but not manganese transport.
• Bled rats showed increased manganese uptake in the brain and iron uptake in the spleen.
• DMT1 transcripts were found in various lung cells, with focal increases in particle-laden macrophages, but expression levels did not correlate with iron status.

Conclusions:

• Pulmonary metal transport and subsequent organ distribution can be modulated by the body's iron status.
• While lung DMT1 expression may play a role, it did not directly correlate with observed pharmacokinetic changes due to altered iron status.
• Iron status significantly influences the potential toxicity and pharmacokinetic behavior of inhaled metals.