Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury

Our plain-English summary of Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury, by H. Prieditis, I.Y. Adamson (Journal of Leukocyte Biology, 1996).

The study

• Authors: H. Prieditis, I.Y. Adamson
• Journal: Journal of Leukocyte Biology
• Published: 1996;59(4):534-8
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Multinucleated giant cells (MGC) are a prominent feature of some chronic inflammatory states in the lung. These cells are formed by macrophage fusion, but how this process relates to the kinetics of alveolar macrophage (AM) production and proliferation is not clear. In this serial study, we compare AM kinetics and MGC formation after instilling carbon, silica, asbestos, bleomycin, and saline into the lungs of mice. Animals were killed up to 16 weeks later with [3H]thymidine injected 1 h before death. Counts of AM and MGC were carried out after bronchoalveolar lavage, and cell labeling was assessed by autoradiography. All test substances induced an inflammatory response with equal AM numbers recovered up to 2 weeks. Subsequently, the number returned to normal after carbon but remained elevated in the other groups. After carbon the lung structure was normal, there was no increase in AM label, and no MGC formed. Bleomycin-injected lungs progressed to fibrosis with only a brief, small increase in AM labeling and no MGC formation. After silica, and particularly asbestos, the lungs showed fibrosis, and many granulomas with large MGC were seen. Lavaged AM from these lungs showed a significant increase in DNA synthesis after 2 weeks, followed by higher numbers of MGC, none of which were labeled. Labeled AM tended to be free of particles, whereas MGC after 4 weeks contained many particles. The results indicate a relationship between AM proliferation and fusion, whereby AM growth appears to be prerequisite for cell infusion and MGC formation as a feature of granulomatous disease.

In plain English

This was an animal experiment in male Swiss Webster mice. The authors placed crocidolite asbestos (0.1 mg, UICC sample), silica (1 mg quartz), carbon black (1 mg), the drug bleomycin (0.15 mg) or saline (the control group) into the windpipe. They killed mice in groups of four at intervals up to 16 weeks. They washed out the lungs to count macrophages (scavenger cells) and multinucleated giant cells, and used a radioactive label to find dividing macrophages. In the first 2 weeks, carbon, bleomycin, silica and asbestos each raised macrophage numbers three to four times. Numbers returned to normal after carbon but stayed raised after the other three. Giant cells were never found in controls or after carbon or bleomycin. They appeared after silica and particularly asbestos, and granulomas (clusters of inflammatory cells) were more prominent after asbestos. Labeling of macrophages was highest after asbestos, roughly 3 percent at 2 to 6 weeks. Giant cells were never labeled. The authors concluded their results were consistent with macrophages fusing into giant cells after dividing. They noted washing may undercount very large giant cells.

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 (serial study in mice comparing lung responses to several instilled substances over time)
• Who was studied: 25-g male Swiss Webster mice, killed in groups of four at intervals up to 16 weeks after instillation. The total number of mice is not stated.
• Exposure: Single intratracheal injection of crocidolite asbestos (0.1 mg of the UICC mixed fiber sample). Comparison groups received silica (1 mg quartz in 0.1 ml saline), carbon black (1 mg) or bleomycin (0.15 mg in 0.1 ml saline), and the control group received 0.1 ml saline.
• Main results:
  • In the saline control group, total cells recovered by lung washing rose slightly at 0.5 weeks but were otherwise at control levels
  • In each of the four test groups (carbon, bleomycin, silica, asbestos), macrophage numbers recovered by lung washing rose three to four times in the first 2 weeks. The authors called this a comparable inflammatory response.
  • After carbon, lavage cell numbers returned to normal after 2 weeks
  • After bleomycin, macrophage numbers stayed above normal to 16 weeks
  • After silica and asbestos, macrophage numbers fell from an early peak but stayed about twice control values to 16 weeks
  • After asbestos, granulomas were more prominent than after silica, with many large giant cells in the alveoli and the interstitium
  • Multinucleated giant cells were never found in control (saline) mice or in mice given carbon or bleomycin
  • In mice given asbestos, the share of labeled (dividing) macrophages was highest, roughly 3 percent in the period 2 to 6 weeks. The symbol before '3%' is garbled in the scan.
  • After bleomycin, macrophage labeling doubled at 1 to 4 weeks and then fell to control values
  • After asbestos, labeled macrophages tended to contain few or no fibers compared with other lavaged macrophages
  • Giant cells were never labeled in any group
  • Giant cells had few particles at earlier stages, but most contained many particles or fibers at later times
• The authors' conclusion: The authors concluded that their in vivo evidence was consistent with the hypothesis that alveolar macrophages fuse into giant cells after dividing
• Limitations the authors state:
  • At later times, giant cell counts from lung washing may underestimate the true total, because some giant cells seemed too large to be washed out

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Macrophage, Bronchoalveolar Lavage (BAL), Fibrosis, Granuloma.

Related studies

• Multinucleated giant cell phenotype in response to stimulation — K.L. Trout, A. Holian (2020)
• Cytotoxicity and multinucleate giant cell formation in Chinese hamster lung fibroblast caused by crocidolite and chrysotile — Y.C. Hong, S.S. Choi (1997)
• Inflammatory cells as a source of airspace extracellular superoxide dismutase after pulmonary injury — R.J. Tan, J.S. Lee, et al. (2006)
• High levels of catalase and glutathione peroxidase activity dampen H2O2 signaling in human alveolar macrophages — A.B. Carter, L.A. Tephly, et al. (2004)
• Contrasting effects of alveolar macrophages and neutrophils on asbestos-induced pulmonary epithelial cell injury — D.W. Kamp, M.M. Dunn, et al. (1994)
• Lung mesothelial cell and fibroblast responses to pleural and alveolar macrophage supernatants and to lavage fluids from crocidolite-exposed rats — I.Y. Adamson, H. Prieditis, et al. (1997)

Browse more research in Journal of Leukocyte Biology, or return to medical research.