Asbestos and Iron

Abstract    Theories of disease pathogenesis following asbestos exposure have developed which focus on a participation of iron. These are integrated to provide a complete assessment of the relationship between asbestos and iron. After exposure, an open network of negatively charged functional groups on the fiber surface complexes host metals with a preference for iron cations. Competition for iron between the host and the asbestos results in a functional iron deficiency. The homeostasis of this metal in the host is modified with the cell response including an upregulation of iron import to correct a loss of the metal to the fiber surface. The biological effects of asbestos develop in response to and are associated with the disruption of iron homeostasis. Cell iron deficiency in the host following fiber exposure activates kinases and transcription factors which are associated with a release of mediators coordinating both inflammatory and fibrotic responses. Relative to the serpentine chrysotile, attempts at clearance of the amphiboles are incomplete resulting only in a translocation to the mesothelial surface of the pleura. Since the biological effect of asbestos is dependent on retention of the fiber, sequestration of iron by the surface, and a functional iron deficiency in the cell, the greater clearance (i.e. decreased persistence) of chrysotile results in its diminished impact. An inability to clear asbestos from the lower respiratory tract initiates a host process of iron biomineralization (i.e. asbestos body formation). Host cells attempt to mobilize the metal sequestered by the fiber surface by producing superoxide at the phagosome membrane. The subsequent ferrous cation is oxidized and undergoes hydrolysis creating poorly crystalline iron oxyhydroxide (i.e. ferrihydrite) included in the coat of the asbestos body.

Impact/Purpose

This manuscript reviews the involvement of iron homeostasis in the biological effects of asbestos.

Citation

Ghio, A., M. Stewart, R. Sangani, E. Pavlisko, AND V. Roggli. Asbestos and Iron. MDPI, Basel, SWITZERLAND, 24(15):12390, (2023). [DOI: 10.3390/ijms241512390]

DOI: Asbestos and Iron