Multinucleated giant cell phenotype in response to stimulation

Our plain-English summary of Multinucleated giant cell phenotype in response to stimulation, by K.L. Trout, A. Holian (Immunobiology, 2020).

The study

• Authors: K.L. Trout, A. Holian
• Journal: Immunobiology
• Published: 2020;225(3):151952
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Macrophages fuse into multinucleated giant cells (MGC) in many pathological conditions. Despite MGC correlations with granulomas, their functional contribution to inflammation is relatively unknown. An in vitro mouse model of IL-4-induced bone marrow-derived macrophage fusion and microfiltration were used to generate enriched MGC and macrophage populations. Phenotypes were compared in response to well-known inflammatory stimuli, including lipopolysaccharide and crocidolite asbestos. Surface markers were assessed by flow cytometry: CD11b, CD11c, F4/80, and MHC II. Secreted cytokines were assessed by multiplex immunoassay: IFN-γ, IL-1β, IL-6, TNF-α, IL-10, IL-13, and IL-33. Results show that MGC maintained macrophage surface protein expression but lost the ability to produce a cytokine response. This suggests a potentially beneficial role of MGC in isolating the host from a foreign body without contributing to excessive inflammation. This study and future research using other stimulants and environments are important to gaining a fundamental MGC cell biology understanding. This will inform approaches to controlling the foreign body response to particle exposure, medical implants, and many diseases associated with granulomas.

Copyright © 2020 Elsevier GmbH. All rights reserved.

In plain English

This was a laboratory study of mouse cells, not of people. The authors grew macrophages, a type of immune cell, from the bone marrow of C57Bl/6 mice aged 10–13 weeks, then used IL-4 to make some fuse into multinucleated giant cells (MGC). Filtering yielded macrophage-enriched and MGC-enriched groups that were still mixed: 33.1% of nuclei lay within MGC in the MGC-enriched group and 0.5% in the other. Cells were left unstimulated or given LPS (a bacterial product), alone or with 25 μg/mL crocidolite asbestos, for 24 hours. Asbestos was not tested on its own. After each cell's marker signal was divided by its nuclear signal, surface markers did not differ significantly between cell types. Cell type significantly affected every cytokine (signaling protein) measured. In MGC, only IL-6 after LPS rose significantly. In macrophages, IL-1β and TNF-α were significantly higher with LPS plus asbestos than with LPS alone. The authors concluded that MGC keep macrophage surface features but lose the ability to promote inflammation. They said this fits a theory that MGC wall off foreign bodies without excessive inflammation, and called for more research.

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: In vitro laboratory experiment on mouse bone marrow-derived macrophages and the multinucleated giant cells (MGC) formed from them
• Who was studied: Cells taken from the bone marrow of C57Bl/6 mice aged 10–13 weeks; results are from three independent replicate groups of mice for each condition
• Exposure: Crocidolite asbestos at 25 μg/mL, given together with LPS at 20 ng/mL, for 24 hours. Comparison groups were unstimulated cells and LPS alone. There was no asbestos-only group.
• Main results:
  • Filtering produced enriched, still-mixed populations: 33.1% fusion in the MGC-enriched population and 0.5% fusion in the macrophage-enriched population. The purity index was increased 71-fold.
  • Before normalization, surface marker fluorescence increased with the number of nuclei in a cell
  • After surface marker fluorescence was normalized to each cell's nuclear fluorescence, expression of CD11b, CD11c, F4/80 and MHC II did not differ significantly between macrophages and MGC
  • LPS treatment significantly increased F4/80 on the cells
  • MHC II increased with LPS and asbestos treatment, but the increase was not statistically significant
  • Cell type (macrophage vs MGC) had a significant effect (p less than 0.05) on all cytokines measured
  • In MGC, the only statistically significant cytokine increase over baseline was IL-6 in the LPS-treated group
  • In macrophages, IL-1β and TNF-α were significantly higher with LPS plus asbestos than with LPS alone
  • In macrophages, IL-6 was not further increased by adding asbestos to LPS
• The authors' conclusion: The authors concluded that MGC appear to keep certain macrophage surface protein characteristics while losing the ability to promote an inflammatory response. They said this fits the theory that MGC form a wall isolating the host from a foreign body without causing excessive inflammation.
• Limitations the authors state:
  • Additional purification steps might have improved purity, but would have reduced total cell numbers
  • More research is needed on how the MGC phenotype may differ with other stimulants and environments

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Granuloma, Inflammation, Crocidolite, Cytokine.

Related studies

• Alveolar macrophage kinetics and multinucleated giant cell formation after lung injury — H. Prieditis, I.Y. Adamson (1996)
• Pleural malignant mesothelioma with osteoclast-like giant cells — H. Itami, C. Ohbayashi, et al. (2010)
• Cytotoxicity and multinucleate giant cell formation in Chinese hamster lung fibroblast caused by crocidolite and chrysotile — Y.C. Hong, S.S. Choi (1997)
• Phenotypes and karyotypes of human malignant mesothelioma cell lines — V. Relan, L. Morrison, et al. (2013)
• Early life exposure to environmental tobacco smoke alters immune response to asbestos via a shift in inflammatory phenotype resulting in increased disease development — T.A. Brown, A. Holian, et al. (2016)
• Activated leukocyte cell-adhesion molecule (ALCAM) promotes malignant phenotypes of malignant mesothelioma — F. Ishiguro, H. Murakami, et al. (2012)

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