Pathogenesis of pleural plaques. Relationship of early cellular response and pathology

Our plain-English summary of Pathogenesis of pleural plaques. Relationship of early cellular response and pathology, by S.A. Sahn, V.B. Antony (The American Review of Respiratory Disease, 1984).

The study

• Authors: S.A. Sahn, V.B. Antony
• Journal: The American Review of Respiratory Disease
• Published: 1984;130(5):884-7
• Cited by: 33 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 000571).

Abstract

To study the initial pleural cellular response to asbestos and to determine the relationship between this response and the development of pleural plaques, a model of asbestos pleurisy was developed in both normal and nitrogen-mustard-treated (neutropenic) New Zealand white rabbits. Animals were rendered neutropenic, as it has been shown that neutropenic rabbits do not develop a macrophage influx in the pleural space after the administration of either BCG or bacteria and that the pathology is different from that in normal rabbits treated in a similar fashion. Intrapleural asbestos induced an exudative effusion in normal animals within 4 h, and there was increased metabolic activity through 120 h, with a fall in pleural fluid pH and PO2 and a rise in pleural fluid PCO2. Neutropenic animals similarly developed an exudative pleural effusion but showed no change in metabolic activity of pleural fluid. Normal rabbits showed a marked cellular influx into the pleural space after asbestos treatment, with a peak total cell count of 27,208/microliters at 24 h; the majority of these cells were polymorphonuclear leukocytes. A macrophage influx occurred at 48 h and peaked at 72 h. By 120 h, lymphocytes were the predominant cell. Nitrogen-mustard-treated animals reached a peak of only 5,442 cells/microliters in the pleural space at 24 h, with a small percentage of polymorphonuclear leukocytes. A macrophage peak did not occur in these animals. There was a marked contrast between groups noted at autopsy. Normal animals developed pleural plaque formation, which was evident by 7 days and completely developed by 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This was an animal experiment in 50 New Zealand white rabbits. Twenty-five were untreated and 25 were given nitrogen mustard, a drug that left them neutropenic (very few neutrophil white blood cells). Each rabbit received 150 mg of UICC chrysotile B asbestos in the right pleural space, the space around the lung. In untreated rabbits, the pleural fluid cell count peaked at 27,208 cells/μl at 24 hours, mostly neutrophils. Macrophages peaked at 68% of cells at 72 hours, and lymphocytes were the main cell by 120 hours. Pleural fluid pH fell over 120 hours, but no animal developed pleural fluid acidosis. Treated rabbits peaked at only 5,442 cells/μl. They had no macrophage influx and no significant change in pleural fluid pH or gas levels. Untreated rabbits developed pleural plaques, evident by 7 days and fully developed by 1 month. Treated rabbits developed no plaques but marked diffuse fibrosis and adhesions, with loose asbestos fibers. The authors concluded that the pleural macrophage appears important in localizing the fibers and in plaque formation. They noted that the model differs from naturally occurring plaques, including a much larger asbestos dose.

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 experiment (rabbit model of asbestos pleurisy, comparing normal and neutropenic animals)
• Who was studied: 50 New Zealand white rabbits weighing 2 to 3 kg. Group 1 was 25 untreated (normal) animals. Group 2 was 25 animals given 1.75 mg/kg of nitrogen mustard intravenously 65 h before the experiment, which made them neutropenic (less than 250 neutrophils/μl). Five animals from each group were killed at 7 days and at 1, 3, 6 and 8 months.
• Exposure: 150 mg of UICC chrysotile B asbestos in 4 ml of saline, instilled through the skin into the right pleural space
• Main results:
  • Normal rabbits: peak pleural fluid total cell count of 27,208/μl at 24 h, mostly polymorphonuclear leukocytes (neutrophils), with a mean absolute neutrophil count of 23,671/μl at 24 h
  • Normal rabbits: macrophages peaked at 68% of the total cell population at 72 h, then fell to 37% by 120 h, when lymphocytes became the predominant cell
  • Normal rabbits: peak pleural fluid protein of 4.5 ± 0.4 g/dl (mean ± SEM) at 48 h. Pleural fluid pH fell progressively over 120 h (p < 0.05), but no animal developed pleural fluid acidosis (pH < 7.30).
  • Nitrogen-mustard-treated rabbits: peak pleural fluid cell count of only 5,442 cells/μl at 24 h, with a small percentage of neutrophils (absolute counts 41 to 435/μl early on). No macrophage peak occurred; macrophages stayed between 5 and 18% of cells.
  • Nitrogen-mustard-treated rabbits: pleural fluid pH and gases did not change significantly through the observation period
  • Normal rabbits developed pleural plaques that were evident by 7 days and completely developed by 1 month. The plaques were on both pleural surfaces, predominantly parietal.
  • Nitrogen-mustard-treated rabbits developed no pleural plaques. Instead they had marked fibrosis and adhesions in the pleural space, with free asbestos fibers not attached to the pleural surface, through 8 months.
• The authors' conclusion: The authors concluded that it appears the pleural macrophage is important in localizing the asbestos fiber and in the eventual formation of the pleural plaque. When too few macrophages are present, disorganized, widespread fibrosis occurs. The neutrophil-macrophage interaction may be pivotal to the development of pleural fibrosis.
• Limitations the authors state:
  • The authors state that this model differs from naturally occurring plaques: the acute asbestos burden was much larger
  • The fibers had not been processed by lung macrophages before entering the pleural space
  • Pleural fluid with many neutrophils was present at the same time, and some plaques formed on the visceral pleura

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Plaques, Pathology, Pleurisy, Macrophage, Pleural Effusion, Autopsy.

Related studies

• Benign asbestos pleurisy in the rabbit. A model for the study of pathogenesis — B.L. Shore, C.C. Daughaday, et al. (1983)
• Pathogenesis of pleurisy, pleural fibrosis, and mesothelial proliferation — A. Herbert (1986)
• Length-dependent pleural inflammation and parietal pleural responses after deposition of carbon nanotubes in the pulmonary airspaces of mice — F.A. Murphy, C.A. Poland, et al. (2013)
• Early response of the visceral pleura following asbestos exposure: an ultrastructural study — R.F. Dodson, J.O. Ford (1985)
• Evidence of a role for mesothelial cell-derived interleukin 8 in the pathogenesis of asbestos-induced pleurisy in rabbits — A.M. Boylan, C. Rüegg, et al. (1992)
• The mechanism of pleural inflammation by long carbon nanotubes: interaction of long fibres with macrophages stimulates them to amplify pro-inflammatory responses in mesothelial cells — F.A. Murphy, A. Schinwald, et al. (2012)

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