Pathogenic effects of inhaled particles and antigens

Our plain-English summary of Pathogenic effects of inhaled particles and antigens, by A.C. Allison (Annals of the New York Academy of Sciences, 1974).

The study

• Author: A.C. Allison
• Journal: Annals of the New York Academy of Sciences
• Published: 1974;221:299-308
• Type of article: Review
• Cited by: 31 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. 002344).

Summary of the article

This review, presented as a symposium paper, summarized evidence on how inhaled particles and antigens damage the lungs, with emphasis on the role of macrophages. The author described how particle size and shape govern deposition. A rat study using radioactive UICC crocidolite found that an average of 35% of inhaled asbestos was deposited, and about 30% of deposited fibre remained in the lungs after 30 days. The author outlined a proposed mechanism of phagocytosis. In the author's experiments with mouse peritoneal macrophages, short chrysotile and crocidolite fibres (<5 µm) were rapidly and completely ingested, while long fibres (>20 µm) were never completely ingested. The review covered how silica and asbestos kill macrophages, linking asbestos toxicity to fibre magnesium content. Animal studies of intrapleural injection indicated that all asbestos types, and some non-asbestos fibres, induced mesotheliomas at about equal frequency if they were in the correct size range. This suggested that fibre dimensions mattered more than chemical composition. The paper discussed fibroblast anchorage dependence and direct stimulation of collagen synthesis by chrysotile in cultured fibroblasts. It also discussed the interaction of asbestos with cigarette smoking in lung cancer. The author reported that immune complexes, at as little as 5 µg/ml, induced selective release of lysosomal enzymes from macrophages. The author speculated that this might help explain fibrosis in extrinsic allergic alveolitis.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was a review of laboratory, animal and human evidence on how inhaled particles, mainly silica and asbestos, and inhaled antigens affect the lungs. It drew on other researchers' studies and on the author's earlier work. The author described an earlier experiment with mouse macrophages. Short chrysotile and crocidolite fibers (under 5 micrometres) were completely taken up by the cells, while long fibers (over 20 micrometres) never were. A cited rat study found that about 35% of inhaled crocidolite was deposited, and about 30% of the deposited fiber remained in the lungs after 30 days. The review reported that chrysotile damaged red blood cells and cultured cells more than other fiber types. Yet in rat studies of injection into the pleura, chrysotile, crocidolite, amosite and some non-asbestos fibers caused mesotheliomas about equally often when of the right size. The author stated that fibrosis and cancer effects appeared more closely tied to fiber length than to chemical make-up, though whether a minimum effective size exists was unresolved. The author also speculated that immune complexes from inhaled antigens might stimulate lung fibrosis through macrophages.

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: Review (symposium paper) of published laboratory, animal and epidemiological work, including the author's own earlier studies
• Who was studied: No study population of its own; the review covered cell cultures (mouse peritoneal macrophages, rabbit lung fibroblasts), experimental animals (rats, hamsters, rabbits) and occupationally exposed humans as described in cited studies
• Exposure: Silica and asbestos (chrysotile, crocidolite, amosite), plus brucite, glass and aluminum oxide fibers; also immune complexes and streptococcal cell wall material in macrophage cultures
• Main results:
  • In the author's earlier study with mouse peritoneal macrophages, short fibers (under 5 micrometres) of either chrysotile or crocidolite were completely taken up, and long fibers (over 20 micrometres) never were
  • In a cited rat study with radioactive UICC crocidolite, an average of 35% of inhaled asbestos was deposited, and after 30 days about 30% of the deposited crocidolite remained in the lungs
  • Chrysotile was reported to be more hemolytic and cytotoxic than other fiber types
  • In rat studies of intrapleural injection or implantation, chrysotile, crocidolite, amosite, brucite, glass and aluminum oxide fibers induced mesotheliomas with approximately equal frequency when in the correct size range
  • Cited work by Stanton suggested fibers about 20 to 200 micrometres long and 0.5 to 5 micrometres in diameter were more effective at inducing mesotheliomas. However, Wagner and Berry found a very short-fibered Canadian chrysotile sample highly efficient
  • In cited cultures of rabbit lung fibroblasts, Rhodesian chrysotile asbestos significantly increased the amount of collagen in the cell mat
  • The author and colleagues found that immune complexes induced selective release of lysosomal enzymes from mouse peritoneal macrophages without loss of cell viability
• The authors' conclusion: The author concluded that fibrogenicity and carcinogenicity appear more closely related to fiber length than to chemical composition. The author speculated that immune complexes formed from inhaled antigens may, through effects on macrophages, stimulate collagen synthesis in the lungs, as a possible explanation for extrinsic fibrosing alveolitis
• Limitations the authors state:
  • The author stated that whether there is a minimum effective fiber size for mesothelioma induction was not yet resolved, and that further work was required
  • The author noted that a reported macrophage factor stimulating collagen synthesis after silica exposure had not been confirmed in several laboratories

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Deposition, UICC, Crocidolite, Phagocytosis, Chrysotile, Mesothelioma, Fibroblast.

Related studies

• Interspecies comparisons of lung responses to inhaled particles and gases — D.B. Warheit (1989)
• Pulmonary macrophages are attracted to inhaled particles through complement activation — D.B. Warheit, L.H. Overby, et al. (1988)
• The NLRP3 inflammasome in pathogenic particle and fibre-associated lung inflammation and diseases — M. Sayan, B.T. Mossman (2016)
• Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125 — S.E. Kabawat, R.C. Bast, et al. (1983)
• Immunoperoxidase localization of keratin proteins, carcinoembryonic antigen, and factor VIII in adenomatoid tumors: evidence for a mesothelial derivation — J.W. Said, G. Nash, et al. (1982)
• Reaction of rat lungs to inhaled chrysotile asbestos following acute and subchronic exposures — B.E. Barry, K.C. Wong, et al. (1983)

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