Ferruginous bodies: implications in the mechanism of fiber and particle toxicity.

Exposures to fibers and particles can be associated with several different lung injuries including bronchitis, bronchiolitis, pneumonitis, pleuritis, pulmonary alveolar proteinosis, pneumoconiosis, mesotheliomas, and lung cancers. The mechanism of biological effect exerted by fibers and particles has not been exactly defined. Exposures to all fibers and particles introduce a solid-liquid interface into the lower respiratory tract. These surfaces all have some concentration of oxygen-containing functional groups that demonstrate a capacity to coordinate iron. Radical generation is catalyzed by this metal resulting in a cascade of cell signaling, transcription factor activation, and mediator release. We propose that the ferruginous body (i.e., a fiber or particle with a coating of both protein and iron) provides direct evidence of a participation of iron in the biological effect of both fibers and particles. It is recommended that an identification of ferruginous bodies in the lung be regarded as support for a metal-catalyzed oxidative stress in the mechanism of cell and tissue injury.