Affordable Access

Macrophage-associated responses to chrysotile.

  • Oberdörster, G
Published Article
The Annals of occupational hygiene
Publication Date
Aug 01, 1994
PMID: 7978983


The different pulmonary macrophage (airway macrophages, alveolar macrophages, interstitial macrophages, intravascular macrophages, pleural macrophages) are an important part of the lungs' defences against non-fibrous and fibrous particles deposited by inhalation. The first line of defence is airway macrophages and alveolar macrophages (AM) which initially interact with deposited chrysotile fibres and subsequently release a number of mediators including growth regulatory and chemotactic proteins, arachidonic acid metabolites, proteases, NO and active oxygen species, all of which can affect--also adversely--specific target cells in the lung. Mechanical clearance via the mucociliary escalator and dissolution of phagocytized fibres in the acidic milieu of the phagolysosome in pulmonary macrophages are further important functions of AM. Chrysotile appears to be more toxic or at least has the same toxicity to AM as amphibole fibres when doses of a similar mass are administered. However, on a fibre number basis chrysotile appears to be less toxic to AM. The importance of the appropriate dose parameter--i.e. fibre mass, number or surface area--needs to be considered in in vitro as well as in in vivo studies. Short chrysotile fibres are cleared from rat lungs very rapidly whereas longer ones are cleared at a much slower rate. This is due to efficient phagocytosis of short fibres by AM accompanied by dissolution in the acidic milieu of the phagolysosome. Prediction of chrysotile clearance in primate lung based on results from rat studies result in an overall retention half-time of approximately 105 days, based on which no long-term accumulation of chrysotile in the primate lung is to be expected. Long-term inhalation studies in baboons exposed to chrysotile confirm the very fast build up of a low steady-state lung burden, consistent with a pulmonary retention half-time for chrysotile of approximately 90 days. Despite the fast clearance and low pulmonary accumulation of chrysotile, the resulting effects, such as asbestosis, were found to be of the same severity in rats as those induced by amphibole exposure. In the amphibole-exposed rats, the fibre lung burden continued to increase with exposure time. The potential contamination of chrysotile with tremolite cannot explain these results since there was no increased pulmonary accumulation of fibres in the chrysotile-exposed rats. Effects due to lung particle overload are not to be expected in long-term chrysotile inhalation studies since no accumulation occurs and one needs to distinguish clearly between a volumetric overload of the AM (not occurring with chrysotile) and failed or partial phagocytosis of long fibres.(ABSTRACT TRUNCATED AT 400 WORDS)


Seen <100 times