Environmental
mineral particles such as
asbestos are responsible for numerous
respiratory diseases. In addition to effects related to their geometry, particles are now assumed to act by triggering an oxidative stress process.
Iron-containing particles, in particular, can produce
oxygen-activated species by oxidizing their
iron. To evaluate the involvement of
iron-containing particles in
respiratory diseases, three
mineral particles (
chrysotile, nemalite, and
hematite) were tested in primary cultures of tracheal epithelium. Because of the ciliary beat, the three
mineral particles were quickly concentrated at the periphery of the mucociliary epithelium, reconstituted in vitro where they induced cellular lesions. Endocytosis of the three types of particles was observed. Cytotoxicity studies have indicated that among the tested particles, the most
cytostatic after 24 hr of treatment was the one that contained more Fe2+ available on the surface, nemalite. Moreover, the effect of nemalite was reduced by pretreatment with
desferrioxamine. As
mineral particles, especially
asbestos, are suspected to induce squamous
metaplasia, we chose to study two specific transformations of the epithelium: the expression of
cytokeratin-13 and the formation of cross-linked envelopes. Under our culture conditions, nemalite and
chrysotile increased the expression of the
cytokeratin-13, a specific marker of squamous
metaplasia, whereas nemalite was the only particle able to strongly induce the formation of cross-linked envelopes. Nemalite was the most
cytostatic particle and the most efficient at inducing squamous
metaplasia. Measures of oxidizing power by electron-spin resonance revealed that nemalite produced the most
oxygen-activated species.(ABSTRACT TRUNCATED AT 250 WORDS)