Interactions of chrysotile asbestos fibres with the complement system

Our plain-English summary of Interactions of chrysotile asbestos fibres with the complement system, by J.M. Saint-Remy, P. Cole (Immunology, 1980).

The study

• Authors: J.M. Saint-Remy, P. Cole
• Journal: Immunology
• Published: 1980;41(2):431-7
• Cited by: 27 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Type A chrysotile fibres (white asbestos) were tested in vitro for activation of the complement system. Fibres were incubated in normal human serum (NHS), factor B-depleted human serum, and normal and C4-deficient guinea-pig sera; the supernates were assayed for the remaining complement activity. Activation of the alternative pathway (AP) was shown in three ways. First, quantitative measurement of factor B; second, kinetic analysis of rabbit red blood cell lysis in whole alternative pathway (AP) and factor B lytic assays; third, qualitative measurement of C3 and factor B conversion by crossed immunoelectrophoresis. No C3 convertase activity could be demonstrated on the fibres but other possible mechanisms of AP activation are discussed. Magnesium itself is not responsible for this activation because acid-treated fibres retain this property. The early classical pathway is not involved as shown by normal whole complement activity of a factor B-depleted human serum and the absence of decrease of C4 functional activity. Knowing that complement proteins are present in pulmonary alveoli, mainly provided by cell synthesis, we suggest that complement activation in vivo may be relevant to the genesis of the chronic inflammation and fibrosis in the lung.

In plain English

In this laboratory study at the Cardiothoracic Institute, Brompton Hospital, London, the authors tested whether chrysotile (white asbestos) fibres activate the complement system, a group of blood proteins involved in immune defence. Type A chrysotile fibres (UICC), some soaked in saline and some acid-treated, were mixed with normal human serum, human serum lacking factor B, and normal and C4-deficient guinea-pig serum. No people or animals were exposed. The fibres activated the 'alternative pathway' of complement. In a red-cell test, serum activity was reduced with as little as 0.5 micrograms of fibre per millilitre, levelling off at 50 micrograms per millilitre. Factor B activity fell by about 50% and did not fall further with up to one hundred-fold more fibre. Acid-treated and autoclaved fibres gave similar results. The 'classical pathway' did not appear to be involved, and no C3-splitting enzyme was found on the fibres. The authors suggested this activation may be one mechanism behind chronic inflammation and fibrosis in the lung. They noted that test-tube results are hard to apply to the living lung.

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: In vitro (laboratory, test-tube) experiment
• Who was studied: No human or animal subjects. Serum samples were used: fresh normal human serum, factor B-depleted human serum, and serum from normal and C4-deficient guinea pigs. The work was done at the Host Defence Unit, Cardiothoracic Institute, Brompton Hospital, London; published 1980.
• Exposure: UICC Type A chrysotile fibres. One portion was kept 7 days in phosphate-buffered saline and another 7 days in 1 M hydrochloric acid, which leaches magnesium. A sample of acid-treated fibres was autoclaved to remove endotoxin. Serial dilutions were incubated with serum; Table 1 covers final concentrations from 0.1 to 250 micrograms per millilitre.
• Main results:
  • In the alternative-pathway kinetic assay with normal human serum, the time needed to lyse 50% of rabbit red cells increased (meaning less complement activity remained) with as little as 0.5 micrograms per millilitre of fibres. A plateau was reached at 50 micrograms per millilitre.
  • Saline-treated and acid-treated fibres gave no differences, except at very low concentrations.
  • Maximal inactivation of the serum was reached in about 30 minutes. Similar results were obtained with normal and C4-deficient guinea-pig serum (data not shown).
  • Factor B activity in human serum fell by about 50% on agarose plates. Increasing the asbestos concentration one hundred-fold produced no further decrease. In a kinetic assay, factor B activity was almost completely lost in 20 minutes.
  • Crossed immunoelectrophoresis showed conversion of C3 and factor B in human serum. At fibre concentrations of 10 to 250 micrograms per millilitre, conversion of each was graded at 25-50%.
  • The amount of factor H in the supernates did not vary.
  • Whole complement activity of normal human serum decreased slightly in proportion to the amount of asbestos. Factor B-depleted serum showed no effect, and C4 activity showed no diminution even at higher doses. The authors took this as evidence that the classical pathway was not involved.
  • No C3 convertase (C3-cleaving enzyme) activity was demonstrated on the fibres.
  • Fibres autoclaved to remove endotoxin gave no difference in results.
• The authors' conclusion: The authors concluded that chrysotile fibres activate the alternative pathway of complement in vitro. They suggested this may be one of the mechanisms generating chronic inflammatory infiltrates in the lung. They also found it 'tempting' to implicate continuous complement activation in vivo in the development of fibrotic changes in the lung.
• Limitations the authors state:
  • The authors state that in vitro results are difficult to extrapolate to in vivo mechanisms, because fibres are physically and chemically modified in the lung.
  • The authors note that chemical and physical modifications of fibres in the body almost certainly influence cellular and humoral responses.
  • The authors could not explain how activation occurs. They had no evidence to confirm or refute adsorption or inhibition of regulatory proteins as the mechanism.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Alveoli, Chronic Inflammation, Fibrosis.

Related studies

• Binding of immunoglobulin and activation of complement by asbestos fibers — P. Hasselbacher (1979)
• C3 activation by monosodium urate monohydrate and other crystalline material — P. Hasselbacher (1979)
• Pulmonary macrophages are attracted to inhaled particles through complement activation — D.B. Warheit, L.H. Overby, et al. (1988)
• Xenopus laevis Oocytes as a Model System for Studying the Interaction Between Asbestos Fibres and Cell Membranes — A. Bernareggi, E. Ren, et al. (2015)
• Interactions of chrysotile and benzopyrene in a human cell culture systems — R.E. Stephens, L.B. Joseph, et al. (1983)
• Wollastonite fibers in vitro generate reactive oxygen species able to lyse erythrocytes and activate the complement alternate pathway — M. Governa, L. Camilucci, et al. (1998)

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