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This Article Full Text Full Text (PDF) All Versions of this Article: 290/6/L1247    most recent 00450.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Heilig, E. A. Articles by Wessling-Resnick, M. Search for Related Content PubMed PubMed Citation Articles by Heilig, E. A. Articles by Wessling-Resnick, M.

Manganese and iron transport across pulmonary epithelium

¹Department of Genetics and Complex Diseases, ²Department of Environmental Health, ³Harvard NIEHS Center for Environmental Health Proteomics Facility, Harvard School of Public Health, Boston, Massachusetts

Submitted 27 October 2005 ; accepted in final form 13 January 2006

Pathways mediating pulmonary metal uptake remain unknown. Because absorption of iron and manganese could involve similar mechanisms, transferrin (Tf) and transferrin receptor (TfR) expression in rat lungs was examined. Tf mRNA was detected in bronchial epithelium, type II alveolar cells, macrophages, and bronchus-associated lymphoid tissue (BALT). Tf protein levels in lung and bronchoalveolar lavage fluid did not change in iron deficiency despite increased plasma levels, suggesting that lung Tf concentrations are regulated by local synthesis in a manner independent of body iron status. Iron oxide exposure upregulated Tf mRNA in bronchial and alveolar epithelium, macrophages, and BALT, but protein was not significantly increased. In contrast, TfR mRNA and protein were both upregulated by iron deficiency. To examine potential interactions with lung Tf, rats were intratracheally instilled with ⁵⁴Mn or ⁵⁹Fe. Unlike ⁵⁹Fe, interactions between ⁵⁴Mn and Tf in lung fluid were not detected. Absorption of intratracheally instilled ⁵⁴Mn from the lungs to the blood was unimpaired in Belgrade rats homozygous for the functionally defective G185R allele of divalent metal transporter-1, indicating that this transporter is also not involved in pulmonary manganese absorption. Pharmacological studies of ⁵⁴Mn uptake by A549 cells suggest that metal uptake by type II alveolar epithelial cells is associated with activities of both L-type Ca²⁺ channels and TRPM7, a member of the transient receptor potential melastatin subfamily. These results demonstrate that iron and manganese are absorbed by the pulmonary epithelium through different pathways and reveal the potential role for nonselective calcium channels in lung metal clearance.

transferrin; bronchoalveolar lavage fluid; macrophages

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