Time course of chemotactic factor generation and the corresponding macrophage response to asbestos inhalation

Our plain-English summary of Time course of chemotactic factor generation and the corresponding macrophage response to asbestos inhalation, by D.B. Warheit, L.H. Hill, G. George, et al (The American Review of Respiratory Disease, 1986).

The study

• Authors: D.B. Warheit, L.H. Hill, G. George, A.R. Brody
• Journal: The American Review of Respiratory Disease
• Published: 1986;134(1):128-33
• Cited by: 78 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Inhalation of asbestos fibers causes a progressive fibrotic lung disease in humans and animals. Pulmonary macrophages are associated with asbestos exposure and have been implicated as significant mediators of the pathogenic process. In previous studies, we showed that macrophages are attracted to sites of asbestos fiber deposition, i.e., alveolar duct bifurcations. We also showed that macrophages accumulated at these sites as the result of asbestos-induced activation of complement proteins on alveolar surfaces, consequently producing C5a, a chemotactic factor for macrophages. In the present study, we have demonstrated the time course of chemotactic factor generation and the corresponding macrophage response in vivo. A complement-dependent chemotactic factor for macrophages was activated during a 3-h exposure to asbestos and reached maximal activity by 3 h postexposure. Macrophage accumulation followed and reached a maximal amount by 24 h postexposure. Rats decomplemented with cobra venom factor exhibited a significant reduction in macrophage accumulation, but the macrophage response ensued when serum complement returned to normal. Approximately 30% of the macrophages lavaged from complement-normal, asbestos-exposed animals contained fibers, whereas only half as many macrophages from decomplemented rats contained asbestos. A small but significant increase in lavaged lung protein was measured in asbestos-exposed animals. Evidence supports the concept that complement proteins on alveolar surfaces are derived from normal transudation of serum components from the pulmonary vasculature. Increased serum transudation could provide a source of alveolar complement that sustains the generation of a chemotactic factor for macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This was a laboratory experiment in male rats, not a study of people. The authors exposed rats to an aerosol of chrysotile asbestos from the Jeffrey Mine in Quebec, at a respirable concentration of about 4 mg/m3, for 1, 3 or 5 hours. They tracked how fast the lungs produced a substance that attracts immune cells called macrophages, and how fast those cells gathered where fibers had landed. With a 3-hour exposure, the attracting substance appeared during exposure, was raised through 24 hours and was back to control levels by 8 days. Macrophage numbers at fiber sites rose from 3 to 24 hours after exposure. Rats whose complement, a blood defense system, was depleted with cobra venom factor 1 or 3 days beforehand had significantly fewer macrophages there. In rats treated 1 day beforehand, 16.3% of washed-out macrophages held fibers, against 30.3% in untreated exposed rats. A 5-hour exposure, but not a 1-hour one, produced a small but significant rise in protein washed out of the lungs at 24 and 48 hours. The authors concluded that macrophages gathered in response to a complement-dependent factor, probably C5a.

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: animal inhalation experiment (rats), including a group pretreated to deplete complement
• Who was studied: Male Crl:CDR(SD) BR rats, 8 to 10 weeks old, studied at the National Institute of Environmental Health Sciences; at least 3 animals per time point for the electron microscopy counts
• Exposure: Aerosolized chrysotile asbestos from the Jeffrey Mine, Quebec, Canada, inhaled for 1, 3 or 5 hours at a respirable mass of approximately 4 mg/m3. Some rats were given 50 units of cobra venom factor 1, 3 or 5 days before exposure to deplete complement.
• Main results:
  • In rats exposed for 3 hours, chemotactic (macrophage-attracting) activity in lung washings was significantly raised compared with sham-exposed rats. It was maintained through 24 hours after exposure and returned to control activity by 8 days.
  • Macrophage numbers at alveolar duct bifurcations (where fibers were first deposited) increased steadily from 3 to 24 hours after a 3-hour exposure, and a peak was maintained through at least 48 hours.
  • Asbestos-exposed rats with normal complement had significantly more macrophages at bifurcations than exposed rats given cobra venom factor 1 or 3 days before exposure. Rats treated 5 days before exposure did not differ statistically from normal exposed rats.
  • In complement-depleted rats, there was no significant increase in macrophage accumulation at 96 hours after exposure, so the reduced response did not appear to be simply delayed.
  • At 48 hours after a 3-hour exposure, these percentages of lavaged macrophages contained asbestos (mean plus or minus SD):
• Untreated exposed rats: 30.3 plus or minus 2.1% (345 cells analyzed).
• Rats given cobra venom factor 1 day before: 16.3 plus or minus 1.4% (228 cells).
• Rats given cobra venom factor 5 days before: 30.9 plus or minus 5.8% (340 cells).
  • Total protein recovered by lung lavage did not differ between sham and asbestos-exposed rats after a 1-hour exposure. After a 5-hour exposure it rose:
• At 24 hours: 1.98 plus or minus 0.28 versus 1.63 plus or minus 0.16 in sham rats.
• At 48 hours: 2.13 plus or minus 0.30 versus 1.59 plus or minus 0.27 in sham rats.
  The units are unreadable in the text.
  • Lung fluids from sham-exposed rats averaged 275 CH50 units of C5 hemolytic complement activity (range 150 to 450 units). None was detectable in fluids from asbestos-exposed rats from immediately after the 3-hour exposure through the following week.
  • Detectable C5 returned to the lungs of exposed rats between 8 and 14 days after exposure.
• The authors' conclusion: The authors concluded that macrophages accumulated at sites of asbestos deposition in response to activation of a complement-dependent chemotactic factor, which they considered probably to be C5a.
• Limitations the authors state:
  • Complement depletion did not completely abolish the macrophage response, so the authors considered it likely that at least one other, unidentified chemotactic signal exists.
  • The authors stated that further studies are needed to establish which macrophage products actually influence the disease process.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Jeffrey mine, Asbestos, Quebec

All asbestos mines

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Macrophage, Asbestos Exposure, Deposition.

Related studies

• Pulmonary macrophages are attracted to inhaled particles through complement activation — D.B. Warheit, L.H. Overby, et al. (1988)
• Chemotactic factor generation by asbestos. Fibre type differences and the effects of leaching — E. Yano, A. Takeuch, et al. (1984)
• Rat alveolar macrophage-derived platelet-derived growth factor is chemotactic for rat lung fibroblasts — A.R. Osornio-Vargas, J.C. Bonner, et al. (1990)
• Asbestos-induced release of a human alveolar macrophage-derived neutrophil chemotactic factor — A.A. Hayes, T.J. Venaille, et al. (1990)
• Neutrophil chemotactic factor release and neutrophil alveolitis in asbestos-exposed individuals — A.A. Hayes, A.H. Rose, et al. (1988)
• Inorganic particles induce secretion of a macrophage homologue of platelet-derived growth factor in a density-and time-dependent manner in vitro — R.M. Schapira, A.R. Osornio-Vargas, et al. (1991)

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