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Cited by 225Cell Adhesion Molecules ResearchPhagocytosis and Immune RegulationCellular Mechanics and Interactions

β1 and β2 Integrins Mediate Adhesion during Macrophage Fusion and Multinucleated Foreign Body Giant Cell Formation

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McNally, Amy K., Anderson, James M.·2002·The American Journal of Pathology
DOI 10.1016/s0002-9440(10)64882-1PMC PMC1850662
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Abstract

An in vitro system of interleukin (IL)-4-induced human monocyte-derived macrophage fusion was used to investigate the cell/substrate adhesive mechanisms that support multinucleated foreign body giant cell (FBGC) formation. Monocytes were cultured for 3 days and IL-4 was added to induce macrophage fusion and FBGC formation by day 7. Functionally defined anti-integrin antibodies demonstrated that initial monocyte adhesion is mediated by beta2 integrins, whereas during the induction of macrophage fusion by IL-4, an additional dependence on beta1 integrins is acquired. The combination of anti-beta1 plus anti-beta2 was most effective, reducing macrophage/FBGC adhesion to 10% of controls. Consistent with integrin-mediated signaling, the tyrosine kinase inhibitor genistein and the phosphatidylinositol-3-kinase inhibitors wortmannin and LY294002 also attenuated macrophage/FBGC adhesion. Confocal microscopic analysis revealed that beta2 integrins are present on monocytes after initial adhesion and are strongly expressed on fusing macrophages, particularly in peripheral cell areas, and on FBGCs. In contrast, beta1 integrins are not detected on monocytes but begin to appear during macrophage development and are strongly expressed on fusing macrophages and FBGCs. For the first time, these results demonstrate the IL-4-induced acquisition of cooperation between beta1 and beta2 integrins in the cell/substrate adhesive interactions that are required for multinucleated FBGC formation.

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Crossref · 10.1016/s0002-9440(10)64882-1

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  • Monocytes initially adhere to most surfaces quite well, but fail to maintain adhesion over time.

    “Monocytes initially adhere to most surfaces quite well, but fail to maintain adhesion over time.[30]”

    From Foreign body reaction to biomaterials (2008) · cites this paper as [30]

    The Initial Monocyte Adhesion section (page unavailable) documents monocytes adhering to culture plates after one hour. The Discussion (page unavailable) also describes adhesion during later macrophage development, but does not say that monocytes fail to maintain adhesion over time or establish that they initially adhere well to most surfaces. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • The dynamics of macrophage fusion into FBGCs is tightly tied to the composition of the protein layer adsorbed to the implant surface and therefore to material properties.

    “The dynamics of the fusion process of macrophages into FBGCs appears to be tightly tied to the composition of the layer of proteins adsorbed to the implants surface, and therefore to the properties of the material itself (McNally and Anderson, 2002).”

    From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as McNally and Anderson, 2002

    The paper’s introduction (page unavailable) says IL-4-induced macrophage fusion is more efficient on RGD-modified surfaces than on standard polystyrene and also requires unidentified adsorbed serum components. The Discussion (page unavailable) proposes interactions with adsorbed proteins. It does not establish that differences in the composition of protein layers on implants determine fusion dynamics or link those differences to specific material properties. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • IL-4 induced fusion is dependent on β1 integrin receptors whereas β2 integrins are involved in the initial monocyte adhesion process.

    “IL-4 induced fusion is dependent on β1 integrin receptors whereas β2 integrins are involved in the initial monocyte adhesion process.[30]”

    From Foreign body reaction to biomaterials (2008) · cites this paper as [30]

    The Discussion reports that β2 integrins mediate initial monocyte adhesion and that adhesion during IL-4-induced fusion acquires a dependence on β1 integrins. It distinguishes adhesion from fusion itself: macrophages remaining after anti-β1 treatment were as competent to fuse as untreated cells. The claim therefore overstates β1's demonstrated role as a requirement for fusion. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • β1 integrins are not initially detected on adherent monocytes but begin to appear during macrophage development and are strongly expressed on fusing macrophages and foreign body giant cells with increased culture time.

    “This phenomenon is time-dependent as β1 integrins are not initially detected on adherent monocytes but begin to appear during macrophage development and are strongly expressed on fusing macrophages and foreign body giant cells with increased culture time.[30]”

    From Foreign body reaction to biomaterials (2008) · cites this paper as [30]

  • β2 integrins are necessary for initial monocyte adhesion to a surface and αM/β2 may play a role in podosome assembly necessary for macrophage adhesion.

    “β2 integrins are necessary for initial monocyte adhesion to a surface and αM/β2 may play a role in podosome assembly necessary for macrophage adhesion.[30]”

    From Foreign body reaction to biomaterials (2008) · cites this paper as [30]

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Cites

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Research works printed but not linked: 2

  1. Berton G, Lowell CA: Integrin signaling in neutrophils and macro- phages. Cell Signal 1999, 11:621-635
  2. Krieger M, Acton S, Ashkenas J, Pearson A, Penman M, Resnick D: Molecular flypaper, host defense. J Biol Chem 1993, 268:4569 -4572

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Authors
McNally, A. K., & Anderson, J. M.
Affiliations
Case Western Reserve University (US)
Corresponding author
Anderson, James M.
ORCID
Anderson, James M.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2002-02
Volume
160
Issue
2
Pages
621-630
ISSN
0002-9440 (ISSN-L)
DOI
10.1016/s0002-9440(10)64882-1
PMC
PMC1850662
OpenAlex
W2022071421
Cited by
225
References
60
Citations by year
2026: 2 · 2025: 5 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 8 · 2017: 6 · 2016: 14 · 2015: 11 · 2014: 9 · 2013: 9 · 2012: 6
FWCI
4.00
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (HL55714, R01HL055714, HL 33849)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Keywords
beta1 integrin, beta2 integrins, macrophage fusion, monocyte adhesion, IL-4, cell-substrate adhesion, integrin signaling, phosphatidylinositol 3-kinase, genistein, wortmannin, LY294002, macrophage differentiation
MeSH terms
Amino Acid Sequence, Cell Adhesion, Cell Fusion, Cells, Cultured, Enzyme Inhibitors, Fibronectins, Humans, Immunohistochemistry, Macrophages, Monocytes, Peptide Fragments, Signal Transduction, Giant Cells, Foreign-Body, Interleukin-4, Microscopy, Confocal, CD18 Antigens, Integrin beta1

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