DISRUPTION OF NORMAL IRON HOMEOSTASIS AFTER BRONCHIAL INSTILLATION OFAN IRON-CONTAINING PARTICLE

The atmosphere constitutes a prime vehicle for the movement and redist ribution of metals. Metal exposure can be associated with an oxidative stress. We tested the hypothesis that, in response to an iron-contain ing particle, the human respiratory tract will demonstrate an increase d expression of both lactoferrin and ferritin as the host attempts to transport and store the metal in a chemically less-reactive form and t herefore diminish the oxidative stress the particle presents. Subjects (n = 22) were instilled with 20 ml of saline and 20 ml of an iron-con taining particle suspended in saline in a right middle lobe bronchus a nd a lingular bronchus, respectively. At either 1, 2, or 4 days after this exposure, the volunteer was lavaged for a sample of the lower res piratory tract, and concentrations of L-ferritin, transferrin, and lac toferrin were measured by enzyme immunoassay, immunoprecipitin analysi s, and enzyme-linked immunosorbent assay (ELISA), respectively. Transf errin receptor was also quantified by ELISA. The concentrations of L-f erritin in the lavage fluid of lung exposed to particles were signific antly increased relative to the levels of the protein in the segment e xposed to saline. Relative to saline instillation, transferrin was sig nificantly diminished after exposure to the iron-containing particle, whereas both lactoferrin and transferrin receptor concentrations in th e segment of the lung exposed to the particle mere significantly eleva ted. We conclude that instillation of an iron-containing particle was associated with a disequilibrium in iron metabolism in the lower respi ratory tract. The response included increased ferritin and lactoferrin concentrations, whereas transferrin concentrations diminished. This c oordinated series of reactions by the host effects a decrease in the a vailability of catalytically reactive iron to likely diminish the cons equent oxidative stress to the human host.