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Galactose supramolecular docking orchestrates macrophage phenotype

Cellular & Molecular Immunology volume 17, pages 1111–1113 (2020)Cite this article

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Macrophages play a key role in the body’s immune functions, including tumor surveillance. Recent studies have indicated that environmental cues and molecular mediators can regulate macrophage polarization via protein–glycan interactions.1 The glycans decorating the Mφ membrane transduce a cascade of feedback signals from the cellular microenvironment into internal signaling pathways, shifting the functional Mφ phenotype that forms the molecular complex.2,3 Therefore, glycans and their derivatives might be attractive targets for controlling Mφ polarization at the supramolecular level. However, the influence of galactose supramolecular docking on cell behavior is currently unknown.

Binding activity represents a miniscule aspect of the interaction of cells with galactose moieties. To test our initial hypothesis that active moieties can induce macrophage polarization, we mimicked the in vivo interaction by incubating resting Mφs (M0 phenotype) with LPS/IFN-γ to induce the M1 phenotype, IL-4 to induce the M2 phenotype, Gal beads or control plain beads.5 The relative transcript levels of the cytokines TNF-α and IL-1β and the scavenger CD163 (which is commonly used to evaluate the M1 or M2 phenotypic status of Mφs6) were measured. As expected, M1 Mφs were found to highly express proinflammatory cytokines (TNF-α and IL-1β), while CD163 expression was suppressed, and the results for M2 Mφs were the opposite (Fig. 1c, d, S4a). Interestingly, incubation of Mφs with Gal beads resulted in obviously increased expression of both TNF-α (Fig. 1c) and IL-1β (Fig. S4a) compared to their levels in the untreated and negative controls. The CD163 transcript levels recorded in Mφ incubated with Gal beads were lower than those in naïve Mφs and negative control-treated Mφs (Fig. 1d). A more advanced step of determining protein production was used to quantify the levels of TNF-α, IL-1β, and IL-10 released from the Mφs when activated by the biochemical factors described above. Similar to the results from the genomic analyses, the data from the biochemical treatments showed that M1 Mφs released more proinflammatory cytokines (TNF-α, Fig. 1e; IL-1β, Fig. S4b), and that IL-4 exposure suppressed these cytokines. As expected, M2 Mφs released more IL-10 than LPS/IFN-γ-induced M1 Mφs (Fig. 1f). These crucial results indicate that, after interacting with galactose moieties, resting Mφs were educated to release a notably greater amount of proinflammatory cytokines, and this release was more profound than that caused by LPS/IFN-γ induction (Fig. 1e, S3b). In addition, IL-10 production was suppressed (Fig. 1f).

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Fig. 1: Galactose docking educated macrophages such that they polarized into a proinflammatory phenotype.

References

  1. Shang, Q. et al. Delivery of adipose-derived stem cells attenuates adipose tissue inflammation and insulin resistance in obese mice through remodeling macrophage phenotypes. Stem Cells Dev. 24, 2052–2064 (2015).

    Article  CAS  Google Scholar 

  2. Su, L. et al. Glycocalyx-mimicking nanoparticles for stimulation and polarization of macrophages via specific interactions. Small 11, 4191–4200 (2015).

    Article  CAS  Google Scholar 

  3. Simone, G. et al. Protein–carbohydrate complex reveals circulating metastatic cells in a microfluidic assay. Small 9, 2152–2161 (2013).

    Article  CAS  Google Scholar 

  4. Zhang, X. M., Pastorino, F. & Simone, G. Microliter chip for sensitive detection of the binding activity of glycans and cognate molecules. Sens. Actuators B-Chem. 273, 342–349 (2018).

    Article  CAS  Google Scholar 

  5. Murray, P. J. et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41, 14–20 (2014).

    Article  CAS  Google Scholar 

  6. Fuchs, A. K. et al. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets. Biomaterials 85, 78–87 (2016).

    Article  CAS  Google Scholar 

  7. MacKinnon, A. C. et al. Regulation of alternative macrophage activation by galectin-3. J. Immunol. 180, 2650–2658 (2008).

    Article  CAS  Google Scholar 

  8. Novak, R., Dabelic, S. & Dumic, J. Galectin-1 and galectin-3 expression profiles in classically and alternatively activated human macrophages. BBA-Gen. Subj. 1820, 1383–1390 (2012).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors want to thank Zhe Wang (School of Life Sciences, Northwestern Polytechnical University) for his support with the fluorescence microscope and Yan Feng (School of Materials Science and Engineering, Northwestern Polytechnical University; Shaanxi materials analysis and research center) for the help with scanning electron microscopy. In addition, the authors would like to thank Sufang Wang (School of Life Sciences, Northwestern Polytechnical University) for sharing comments about the manuscript. The authors are thankful for the support from the Foreigner Students Exchanging Program between the Northwestern Polytechnical University and Avans University. This work was supported by the National Natural Science Foundation of China (11722220, 11672246, and 11472224) and Fundamental Research Funds for the Central Universities (G2016KY0302 and G2017KY0320). N. Zhang and G. Simone contributed equally to this work.

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  1. These authors contributed equally: Nu Zhang, Giuseppina Simone

Authors and Affiliations

  1. School of Life Sciences, Northwestern Polytechnical University, 710072, Xi’an Shaanxi, China

    Nu Zhang, Xinmin Zheng, Yidan Zhou & Hui Yang

  2. Center of Special Environmental Biomechanics & Biomedical Engineering, Northwestern Polytechnical University, 710072, Xi’an Shaanxi, China

    Nu Zhang, Xinmin Zheng, Yidan Zhou & Hui Yang

  3. The Ministry of Education Key Laboratory of Micro/Nano Systems for Aerospace, School of Mechanical Engineering, Northwestern Polytechnical University, 127 West Youyi Road, 710072, Xi’an Shaanxi, China

    Guus Couvee, Ferry Wolterboer, Oole Van deDonk & Giuseppina Simone

  4. Department of Mechanical Engineering, Avans University of Applied Sciences, Lovensdijkstraat 61 - 63, Breda Noord-Brabant, 4818 AJ, Breda, Netherlands

    Guus Couvee, Ferry Wolterboer & Oole Van deDonk

  5. Medical Research Institute, Northwestern Polytechnical University, 710072, Xi’an Shaanxi, China

    Hui Yang

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Correspondence to Hui Yang or Giuseppina Simone.

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Zhang, N., Zheng, X., Couvee, G. et al. Galactose supramolecular docking orchestrates macrophage phenotype. Cell Mol Immunol 17, 1111–1113 (2020). https://doi.org/10.1038/s41423-019-0358-2

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