Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length

Our plain-English summary of Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length, by G. Forget, M.J. Lacroix, R.C. Brown, et al (Environmental Research, 1986).

The study

• Authors: G. Forget, M.J. Lacroix, R.C. Brown, P.H. Evans, P. Sirois
• Journal: Environmental Research
• Published: 1986;39(1):124-35
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The effect of glass fibers on rat alveolar macrophages was studied with a new perifusion technique which allows the sequential determination of cell-derived inflammatory mediators as well as estimation of cell viability and aggregation at the end of the incubation period. Our results showed that glass fibers induced dose-dependent release of prostaglandins and beta-glucuronidase from macrophages and the aggregation and death of these cells. These deleterious effects were clearly related to the length of the fibers, with the longer fibers (greater than or equal to 4-5 micron) being more active than the shorter ones (less than 3 micron). Furthermore, a short exposure of 1 hr followed by an 18-hr perifusion induced the same inflammatory and toxic effects on the macrophages as did leaving the fibers undisturbed for the complete 18-hr perifusion. It is concluded that glass fibers produce effects in cultures of rat alveolar macrophages qualitatively similar to those of asbestos, and that fiber length appears to be a critical determinant of toxicity.

In plain English

This laboratory study exposed rat alveolar macrophages, immune cells washed from rat lungs, to Johns-Manville code 100 glass fibers in an 18-hour culture system called perifusion. The fibers killed cells and caused clumping, more so at higher doses. At 10 micrograms per ml, dead cells rose to 25.8% from 9.4% in controls. At 50 and 100 micrograms per ml, cell death was 3.3 and 4.5 times control. The fibers also increased release of the enzyme beta-glucuronidase and of prostaglandin E, an inflammatory mediator. Replacing the fiber-containing medium after 1 hour gave cell death, clumping and enzyme release similar to leaving fibers in for 18 hours. The authors considered this evidence the fibers had been engulfed or had interacted with the cells so that they could not be removed. Fibers shortened by milling were still toxic but less so. The most milled sample, with all fibers examined under 3 micrometers long, caused 27.1% cell death against 11.3% in controls. The authors concluded the effects were qualitatively similar to those of asbestos and that fiber length appeared a critical determinant of toxicity.

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: laboratory (in vitro) experiment on rat cells in culture, using a perifusion culture system
• Who was studied: Alveolar macrophages from rats, obtained by bronchoalveolar lavage; the cell suspension was 97% alveolar macrophages. Results were means of at least four separate observations. The number of rats is not given. Work was done at the Université de Sherbrooke (Quebec, Canada) and the MRC Pneumoconiosis Unit (UK); received May 1984.
• Exposure: Johns-Manville code 100 microglass fiber, either unmilled or ball milled for 15, 30 or 60 min to shorten the fibers. Concentrations were 10, 50 or 100 micrograms per ml. Exposure was either a 1-hour pulse, after which the fiber-containing medium was replaced before an 18-hour perifusion, or continuous for the full 18 hours.
• Main results:
  • Unmilled glass fibers at 10 micrograms per ml for 18 hr: dead cells were 25.8 ± 0.74%, against a control level of 9.4 ± 0.8% (p less than or equal to 0.01).
  • Cell death at 50 and 100 micrograms per ml was 3.3-fold and 4.5-fold higher than control levels, respectively (p less than or equal to 0.01).
  • Cell clumping (aggregation), from a control level of 8.6 ± 0.9%, rose by a factor of 3, 3.9 and 7.7 at 10, 50 and 100 micrograms per ml, respectively.
  • After subtracting control levels, cumulative 18-hour beta-glucuronidase release was 2.3 times (at 50 micrograms per ml) or 6.5 times (at 100 micrograms per ml) higher than at 10 micrograms per ml.
  • At 50 micrograms per ml, cell mortality was the same when the fiber-containing medium was replaced after 1 hour (pulse) and when fibers were left for the full 18 hours (34.9 ± 0.7% and 34.6 ± 1.2%). Aggregation and beta-glucuronidase release were also similar for the two exposure durations.
  • The authors interpreted the pulse result as evidence that the fibers had been engulfed by the cells or had interacted with them so that they could not be removed.
  • With 50 micrograms per ml of fibers, prostaglandin E output rose to up to three times that of unstimulated cultures, peaking after 8 hours. Basal release was 0.25 to 0.6 ng per million cells.
  • Milling shortened the fibers without reducing their diameter.
  • In the most milled sample, all fibers examined were under 3 micrometers long; it still caused 27.1 ± 0.3% cell mortality, against 11.3 ± 1.0% in controls. Toxicity differed significantly between the samples, with shorter fibers less toxic.
  • Cumulative beta-glucuronidase release did not differ significantly between unmilled fibers and fibers milled for 15 min, nor between those milled for 30 and 60 min. The 15-min sample differed significantly from both the 30- and 60-min samples.
  • The fiber samples milled for 30 and 60 minutes contained no fibers longer than 6 micrometers.
• The authors' conclusion: The authors concluded that the toxic and inflammatory effects of the glass fibers on rat alveolar macrophages were qualitatively similar to those of asbestos fibers in similar experiments, and that these responses were clearly related to fiber length, with longer fibers more active than shorter ones.
• Limitations the authors state:
  • The authors had no experimental data linking the effects to the cells engulfing (phagocytosing) the fibers.
  • The authors noted that the biological significance of macrophage clumping is not fully understood.

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Fiber Length, Macrophage.

Related studies

• An adherent cell perifusion technique to study the overall and sequential response of rat alveolar macrophages to toxic substances — G. Forget, M.J. Lacroix, et al. (1983)
• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)
• Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization — K. Donaldson, X.Y. Li, et al. (1992)
• Phagocytosis of asbestos fibers by human pulmonary alveolar macrophages — T. McLemore, M. Corson, et al. (1979)
• Asbestos-induced alveolar injury. Evidence for macrophage-derived PDGF as a mediator of the fibrogenic response — J.C. Bonner, A.R. Brody (1991)
• Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis — I. Lemaire, H. Beaudoin, et al. (1986)

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