Disruption of normal iron homeostasis after bronchial instillation of an iron-containing particle.
The atmosphere constitutes a prime vehicle for the movement and redistribution of metals. Metal exposure can be associated with an oxidative stress. We tested the hypothesis that, in response to an iron-containing particle, the human respiratory tract will demonstrate an increased expression of both lactoferrin and ferritin as the host attempts to transport and store the metal in a chemically less-reactive form and therefore diminish the oxidative stress the particle presents. Subjects (n = 22) were instilled with 20 ml of saline and 20 ml of an iron-containing particle suspended in saline in a right middle lobe bronchus and a lingular bronchus, respectively. At either 1, 2, or 4 days after this exposure, the volunteer was lavaged for a sample of the lower respiratory tract, and concentrations of L-ferritin, transferrin, and lactoferrin were measured by enzyme immunoassay, immunoprecipitin analysis, and enzyme-linked immunosorbent assay (ELISA), respectively. Transferrin receptor was also quantified by ELISA. The concentrations of L-ferritin in the lavage fluid of lung exposed to particles were significantly increased relative to the levels of the protein in the segment exposed to saline. Relative to saline instillation, transferrin was significantly diminished after exposure to the iron-containing particle, whereas both lactoferrin and transferrin receptor concentrations in the segment of the lung exposed to the particle were significantly elevated. We conclude that instillation of an iron-containing particle was associated with a disequilibrium in iron metabolism in the lower respiratory tract. The response included increased ferritin and lactoferrin concentrations, whereas transferrin concentrations diminished. This coordinated series of reactions by the host effects a decrease in the availability of catalytically reactive iron to likely diminish the consequent oxidative stress to the human host.
Ghio
A J
AJ
National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina.
Carter
J D
JD
Richards
J H
JH
Brighton
L E
LE
Lay
J C
JC
Devlin
R B
RB
D000293:Adolescent; D000328:Adult; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005293:Ferritins / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D007781:Lactoferrin / Q000378:metabolism; D008297:Male; D008863:Microspheres; D018384:Oxidative Stress; D011990:Receptors, Transferrin / Q000378:metabolism; D012016:Reference Values
D011990:Receptors, Transferrin; D005293:Ferritins; D007501:Iron; D007781:Lactoferrin