Mechanisms of macrophage accumulation in the lungs of asbestos-exposed subjects

Our plain-English summary of Mechanisms of macrophage accumulation in the lungs of asbestos-exposed subjects, by J.R. Spurzem, C. Saltini, W. Rom, et al (The American Review of Respiratory Disease, 1987).

The study

• Authors: J.R. Spurzem, C. Saltini, W. Rom, R.J. Winchester, R.G. Crystal
• Journal: The American Review of Respiratory Disease
• Published: 1987;136(2):276-80
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chronic asbestos exposure is associated with the accumulation of mononuclear phagocytes in the lower respiratory tract. This process can be both protective and injurious, since macrophages can aid in asbestos clearance yet also modulate structural derangements of the alveolar walls. To understand why macrophages accumulate in the lungs of asbestos-exposed persons, 2 possible mechanisms were evaluated using alveolar macrophages from subjects with histories of chronic high exposure to airborne asbestos: enhanced recruitment of blood monocytes to the lung, and an increased rate of replication of macrophages in situ. Monoclonal antibody analysis with antibodies that detect surface antigens on the majority of circulating blood monocytes but only on a minority of mature alveolar macrophages demonstrated that an increased proportion of alveolar macrophages of asbestos workers expressed monocyte lineage antigens, suggesting the presence of "young" newly recruited macrophages and thus enhanced recruitment. Culture of the alveolar macrophages from these subjects with [3H]thymidine followed by autoradiography demonstrated an increased proportion of alveolar macrophages synthesizing DNA, suggesting the macrophages are replicating at an increased rate in situ. These observations are consistent with the concept that both enhanced recruitment of blood monocytes and increased local proliferation of alveolar macrophages contribute to the accumulation mononuclear phagocytes in the lung of persons with chronic asbestos exposure.

In plain English

This laboratory study asked why scavenger cells called alveolar macrophages build up in the lungs of people with long-term asbestos exposure. The authors collected lung cells by washing (bronchoalveolar lavage) from 14 insulators or pipefitters with 20 years or more of asbestos exposure and from 14 younger, healthy nonsmoking volunteers. They used three antibodies for markers found on most blood monocytes but only a minority of mature lung macrophages. These markers were more common on the workers' lung macrophages (p less than 0.05), which the authors took to suggest newly recruited cells. Amosite, crocidolite and chrysotile fibers added to volunteers' cells in the laboratory did not raise these markers. During 18 hours in culture, a significantly larger share of macrophages from most workers than from volunteers copied their DNA, a step in cell division (p less than 0.05). The authors concluded that their observations suggest both more recruitment from the blood and more local multiplication contribute. Comparisons among subgroups of workers found no statistically significant differences in these markers, but the authors noted too few had abnormal lung function for general conclusions comparing those with and without asbestosis.

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: Cross-sectional laboratory comparison of lung lavage cells from asbestos-exposed workers and normal volunteers, plus in vitro (cell culture) experiments with asbestos fibers
• Who was studied: 14 chronically exposed asbestos workers (mean age 56 ± 3 yr; 4 lifetime nonsmokers, 10 ex-smokers who had quit at least 5 yr before; 8 had chest radiographs of ILO 1/0 or greater; 4 had restrictive lung function) compared with 14 normal nonsmoking volunteers (mean age 32 ± 2 yr). Location: National Institutes of Health, Bethesda, Maryland; dates of study not stated.
• Exposure: Workers: 20 years or more of occupational asbestos exposure as insulators or pipefitters; fiber type not stated. In vitro: 500 ug autoclaved amosite, crocidolite, and short and intermediate length chrysotile added to cell cultures
• Main results:
  • Blood monocytes: in both the asbestos-exposed and normal subjects, the majority were positive for the monocyte-lineage antigens, with no significant difference between groups (p > 0.4, all comparisons)
  • Alveolar macrophages: all 3 antibodies detected increased expression of monocyte-lineage surface antigens on macrophages from asbestos-exposed subjects compared with normal subjects (p <0.05, all comparisons). The authors interpreted this as suggesting young, newly recruited macrophages
  • Within the asbestos-exposed group, comparisons of monocyte-lineage antigen expression showed no statistically significant differences (p >0.1, all comparisons) between lifetime nonsmokers and ex-smokers, between those with abnormal and normal radiographs, between those with and without rales, or between those with restrictive and normal lung function
  • In vitro, blood monocytes from normal volunteers cultured for 3 days with each form of asbestos showed no increase in surface antigen expression. For one antibody (M0-p9 in the scanned text), the asbestos-treated cells showed less expression (p < 0.05)
  • In vitro, alveolar macrophages from normal volunteers cultured with each type of asbestos fiber showed no increase in surface antigen expression. The authors concluded that a direct effect of asbestos did not appear to account for the increased antigen expression seen in the workers
  • DNA synthesis was measured in lavage cells during an 18-hour culture. Macrophages from both groups were synthesizing DNA. Compared with normal subjects, the majority of asbestos-exposed workers had a significantly increased proportion of alveolar macrophages in the S phase of the cell cycle (p < 0.05)
• The authors' conclusion: The authors concluded that their observations suggest that both enhanced recruitment of blood monocytes and enhanced proliferation of alveolar macrophages contribute to the accumulation of these cells in the lower respiratory tract of persons chronically exposed to high concentrations of asbestos
• Limitations the authors state:
  • Too few subjects had abnormal lung function to draw general conclusions comparing workers with and without asbestosis
  • The asbestos workers and the normal control subjects were not age-matched. The authors stated they had not noted significant age-related changes in lavage characteristics among nonsmoking normal volunteers

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Asbestos Exposure, Alveolar Macrophage, Monoclonal Antibody.

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