Macrophage-associated responses to chrysotile

Our plain-English summary of Macrophage-associated responses to chrysotile, by G. Oberdörster (The Annals of Occupational Hygiene, 1994).

The study

• Author: G. Oberdörster
• Journal: The Annals of Occupational Hygiene
• Published: 1994;38(4):601-15, 421-2
• Cited by: 38 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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)

In plain English

This brief workshop overview (1993) reviewed published studies on how lung scavenger cells (macrophages) respond to inhaled chrysotile asbestos, without new experiments. From rat data (Coin et al., 1992), the author calculated that short chrysotile fibres, which macrophages can engulf, dissolve quickly and longer ones far more slowly. Assuming similar dissolution across species and a single clearance rate, the author predicted a primate-lung retention half-time of about 105 days for fibres dissolving at 0.005 per day (the longest-fibre rate), noting some fibres might stay longer. The author fitted baboon data (Rendall, 1988) with a half-time of about 90 days. In rats (Wagner et al., 1974), chrysotile built up far less than amphiboles (about 1 mg versus about 15 mg), yet equal cumulative exposure gave similar asbestosis grades. The author argued that tremolite contamination was unlikely to explain this. In rats (Davis et al., 1991), adding titanium dioxide or quartz dust to chrysotile or amosite exposure increased lung tumours and mesotheliomas compared with asbestos alone. The author concluded that efficient fibre removal and low persistence do not prevent long-term fibrosis and lung tumours.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: narrative review (brief overview paper read at a workshop); no new data, apart from the author's own calculations based on published results
• Who was studied: No study population of its own. The article reviewed published studies in rats, mice, baboons, dogs, sheep, isolated macrophages from several species, and some human lavage and tissue studies. It was presented at a workshop in Jersey, Channel Islands, 14-17 November 1993.
• Exposure: Inhaled chrysotile asbestos, compared in the reviewed studies with amphiboles (amosite, crocidolite), and combined with titanium dioxide or quartz dust in mixed-dust studies
• Main results:
  • In rats (study by Coin et al., 1992, as described), chrysotile fibres up to about 8 micrometres long were cleared with retention half-times of about 30 to 8 days. Fibres longer than 16 micrometres had a retention half-time of about 115 days.
  • The author's own calculations from those rat data estimated fast dissolution for chrysotile fibres short enough for macrophages to engulf, and much slower dissolution for longer fibres. The table gives a dissolution rate of 0.005 per day for fibres longer than 16 micrometres.
  • The author assumed that dissolution rates do not differ markedly between mammalian species. On that basis the author predicted that chrysotile fibres dissolving at 0.005 per day would have an overall retention half-time of about 105 days in the primate lung. This prediction assumed a single (mono-exponential) clearance rate.
  • In baboons (Rendall, 1988, as described), chrysotile lung levels levelled off after about 12 months of exposure, equivalent to a retention half-time of about 90 days. For glass fibres, amosite and crocidolite in baboons, the retention half-times were about 200 to 1500 days.
  • None of the chrysotile-exposed baboons survived the 36 months of exposure, unlike the baboons exposed to other fibre types. Whether this was caused by chrysotile toxicity or by other factors was not known.
  • In rats (Wagner et al., 1974, as described), about 15 mg of amphibole asbestos built up in the lungs over 24 months of exposure, compared with a maximum of about 1 mg for chrysotile. Despite this, equal cumulative exposure to the two asbestos types produced a similar severity of pulmonary fibrosis (asbestosis) and also of lung tumours.
  • The author argued that tremolite contaminating the chrysotile was unlikely to explain the chronic effects in the Wagner et al. rat study.
  • The author judged lung particle 'overload' from chronic chrysotile inhalation to be highly unlikely.
  • Davis et al. (1991), as described, exposed rats for 1 year to chrysotile or amosite (10 mg per cubic metre) plus titanium dioxide or quartz. Compared with asbestos alone, the dust co-exposure increased lung tumours and mesotheliomas for both asbestos types.
• The authors' conclusion: The author concluded that even effective removal of fibres by alveolar macrophages, resulting in low biopersistence of fibres in the lung, does not prevent adverse long-term effects such as fibrosis and lung tumours.
• Limitations the authors state:
  • The predicted primate retention half-time assumed a single clearance rate and did not account for possibly longer retention of a small portion of fibres.
  • The extrapolation from rats to the human lung assumed that dissolution rates do not differ markedly between mammalian species.
  • The cause of the high mortality in the chrysotile-exposed baboons was not known.
  • No data were available on whether mixed dust exposure affects the dissolution of chrysotile.
  • In vitro studies generally do not consider the actual dose of fibres taken up by cells.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite, Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Macrophage, Chrysotile, Alveolar Macrophage, Interstitial, Mucociliary Clearance, Phagolysosome, Amphibole Group, Phagocytosis.

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