EFFECT OF MINERAL PARTICLES CONTAINING IRON ON PRIMARY CULTURES OF RABBIT TRACHEAL EPITHELIAL-CELLS - POSSIBLE IMPLICATION OF OXIDATIVE STRESS

Environmental mineral particles such as asbestos are responsible for n umerous 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 invo lvement of iron-containing particles in respiratory diseases, three mi neral particles (chrysotile, nemalite, and hematite) were tested in pr imary cultures of tracheal epithelium. Because of the ciliary beat, th e three mineral particles were quickly concentrated at the periphery o f the mucociliary epithelium, reconstituted in vitro where they induce d cellular lesions. Endocytosis of the three types of particles was ob served. Cytotoxicity studies have indicated that among the tested part icles, the most cytostatic after 24 hr of treatment was the one that c ontained more Fe2+ available on the surface, nemalite. Moreover, the e ffect of nemalite was reduced by pretreatment with desferrioxamine. As mineral particles, especially asbestos, are suspected to induce squam ous metaplasia, we chose to study two specific transformations of the epithelium: the expression of cytokeratin-13 and the formation of cros s-linked envelopes. Under our culture conditions, nemalite and chrysot ile 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 squam ous metaplasia. Measures of oxidizing power by electron-spin resonance revealed that nemalite produced the most oxygen-activated species. Th is observation and its reduced toxicity by the desferrioxamine treatme nt suggest that nemalite could act on rabbit tracheal epithelial cells by an oxidative stress process.