Abnormally high incidences of
asbestos-related
pulmonary disease have been reported in residents of Libby, Montana, because of occupational and environmental exposure to
asbestos-contaminated
vermiculite. The mechanism by which Libby
amphibole (LA) causes
pulmonary injury is not known. The purpose of this study is to compare the cellular stress responses induced in primary human airway epithelial cells (HAECs) exposed to a respirable size fraction (≤ 2.5 μm) of Libby
amphibole (LA(2.5)) to a similar size fraction of a reference
amphibole sample
amosite (AM(2.5)). HAEC were exposed to 0, 2.64, 13.2, or 26.4 μg/cm(2) AM(2.5) or LA(2.5) or to equivalent doses of unfractionated
amosite (AM) or LA for 2 or 24 h. Comparable
messenger RNA transcript levels were observed for
interleukin-8,
cyclooxygenase-2, and
heme oxygenase-1 in HAEC following a 24-h exposure to AM or LA. Conversely, exposure to AM(2.5) resulted in a 4- to 10-fold greater induction in these proinflammatory mediators compared with LA(2.5) after 24 h. Evaluation of the expression of 84 additional genes involved in cellular stress and toxicity responses confirmed a more robust response for AM(2.5) compared with LA(2.5) on an equal mass basis. Differences in total surface area (
TSA) by gas adsorption, total particle number, or
oxidant generation by the size-fractionated particles did not account for the observed difference in response. In summary, AM(2.5) and LA(2.5) are at least as potent in stimulating production of proinflammatory
cytokines as unfractionated AM and LA. Interestingly, AM(2.5) was more potent at inducing a proinflammatory response than LA(2.5). This difference could not be explained by differences in
mineral contamination between the two samples,
TSA, or
oxidant generation by the samples.