Details

Autor(en) / Beteiligte

• Heilig, Elizabeth A
• Thompson, Khristy J
• Molina, Ramon M
• Ivanov, Alexander R
• Brain, Joseph D
• Wessling-Resnick, Marianne

Titel

Manganese and iron transport across pulmonary epithelium

Ist Teil von

• American journal of physiology. Lung cellular and molecular physiology, 2006-06, Vol.290 (6), p.L1247-L1259

Ort / Verlag

United States

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• 1 Department of Genetics and Complex Diseases, 2 Department of Environmental Health, 3 Harvard 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 54 Mn or 59 Fe. Unlike 59 Fe, interactions between 54 Mn and Tf in lung fluid were not detected. Absorption of intratracheally instilled 54 Mn 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 54 Mn uptake by A549 cells suggest that metal uptake by type II alveolar epithelial cells is associated with activities of both L-type Ca 2+ 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 Address for reprint requests and other correspondence: M. Wessling-Resnick, Dept. of Genetics and Complex Diseases, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115 (e-mail: wessling{at}hsph.harvard.edu )