Am. J. Respir. Cell Mol. Biol., Volume 20, Number 4, April, 1999 631-642

Cellular and Biochemical Response of the Human Lung after Intrapulmonary Instillation of Ferric Oxide Particles

John C. Lay, William D. Bennett, Andrew J. Ghio, Philip A. Bromberg, Daniel L. Costa, Chong S. Kim, Hillel S. Koren, and Robert B. Devlin

Center for Environmental Medicine and Lung Biology, University of North Carolina; Clinical Research Branch, Human Studies Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Chapel Hill; and Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina

Bronchoalveolar lavage (BAL) was used to sample lung cells and biochemical components in the lung air spaces at various times from 1 to 91 d after intrapulmonary instillation of 2.6 µm-diameter iron oxide particles in human subjects. The instillation of particles induced transient acute inflammation during the first day post instillation (PI), characterized by increased numbers of neutrophils and alveolar macrophages as well as increased amounts of protein, lactate dehydrogenase, and interleukin-8 in BAL fluids. This response was subclinical and was resolved within 4 d PI. A similar dose-dependent response was seen in rats 1 d after intratracheal instillation of the same particles. The particles contained small amounts of soluble iron (240 ng/mg) and possessed the capacity to catalyze oxidant generation in vitro. Our findings indicate that the acute inflammation after particle exposure may, at least partially, be the result of oxidant generation catalyzed by the presence of residual amounts of ferric ion, ferric hydroxides, or oxyhydroxides associated with the particles. These findings may have relevance to the acute health effects associated with increased levels of ambient particulate air pollutants.

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