Skip to main content

Advertisement

SpringerLink
Log in

Mesenchymal Stem Cells Alleviate Experimental Asthma by Inducing Polarization of Alveolar Macrophages

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The reparative and immunoregulatory properties of mesenchymal stromal cells (MSCs) have made them attractive candidates for cellular therapy. However, the underlying mechanism of the effects of transplanted MSCs on allergic asthma remains elusive. Here, we show that administration of MSCs isolated from human bone marrow provoked a pronounced polarization in alveolar macrophages to M2 subtypes, rather than induced an increase in the total macrophage number, and efficiently inhibited hallmark features of asthma, including airway hyperresponsiveness and eosinophilic accumulation. Moreover, transforming growth factor beta (TGF-β) signaling pathway appeared to mediate the effects of MSCs on macrophage polarization and subsequently the inhibition of hallmark features of asthma. Inhibition of TGF-β signaling was sufficient to inhibit the macrophage polarization in response to MSCs and consequently reserved the inhibitory effects of macrophage polarization on hallmark features of asthma. Collectively, our data demonstrate that human MSCs have immunosuppressive activity on asthma, which is mediated by TGF-β-signaling-dependent alveolar macrophage polarization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Zipori, D. 2004. Mesenchymal stem cells: harnessing cell plasticity to tissue and organ repair. Blood Cells, Molecules & Diseases 33: 211–215.

    Article  CAS  Google Scholar 

  2. Uccelli, A., L. Moretta, and V. Pistoia. 2008. Mesenchymal stem cells in health and disease. Nature Reviews Immunology 8: 726–736.

    Article  CAS  PubMed  Google Scholar 

  3. Fischer, U.M., M.T. Harting, F. Jimenez, W.O. Monzon-Posadas, H. Xue, S.I. Savitz, et al. 2009. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells and Development 18: 683–692.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Holgate, S.T. 2008. Pathogenesis of asthma. Clinical and Experimental Allergy 38: 872–897.

    Article  CAS  PubMed  Google Scholar 

  5. Holgate, S.T. 2008. The airway epithelium is central to the pathogenesis of asthma. Allergology International: Official Journal of the Japanese Society of Allergology 57: 1–10.

    Article  CAS  Google Scholar 

  6. Bonfield, T.L., M. Koloze, D.P. Lennon, B. Zuchowski, S.E. Yang, and A.I. Caplan. 2010. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. American Journal of Physiology - Lung Cellular and Molecular Physiology 299: L760–L770.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Sica, A., and A. Mantovani. 2012. Macrophage plasticity and polarization: in vivo veritas. Journal of Clinical Investigation 122: 787–795.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Martinez, F.O., L. Helming, and S. Gordon. 2009. Alternative activation of macrophages: an immunologic functional perspective. Annual Review of Immunology 27: 451–483.

    Article  CAS  PubMed  Google Scholar 

  9. Gordon, S., and F.O. Martinez. 2010. Alternative activation of macrophages: mechanism and functions. Immunity 32: 593–604.

    Article  CAS  PubMed  Google Scholar 

  10. Xiao, X., I. Gaffar, P. Guo, J. Wiersch, S. Fischbach, L. Peirish, et al. 2014. M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7. Proceedings of the National Academy of Sciences of the United States of America 111: E1211–E1220.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Ricardo, S.D., H. van Goor, and A.A. Eddy. 2008. Macrophage diversity in renal injury and repair. Journal of Clinical Investigation 118: 3522–3530.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Pull, S.L., J.M. Doherty, J.C. Mills, J.I. Gordon, and T.S. Stappenbeck. 2005. Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proceedings of the National Academy of Sciences of the United States of America 102: 99–104.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Tropel, P., D. Noel, N. Platet, P. Legrand, A.L. Benabid, and F. Berger. 2004. Isolation and characterisation of mesenchymal stem cells from adult mouse bone marrow. Experimental Cell Research 295: 395–406.

    Article  CAS  PubMed  Google Scholar 

  14. Zhou, B., X.C. Cao, Z.H. Fang, C.L. Zheng, Z.B. Han, H. Ren, et al. 2007. Prevention of diabetic microangiopathy by prophylactic transplant of mobilized peripheral blood mononuclear cells. Acta Pharmacologica Sinica 28: 89–97.

    Article  CAS  PubMed  Google Scholar 

  15. Inman, G.J., F.J. Nicolas, J.F. Callahan, J.D. Harling, L.M. Gaster, A.D. Reith, et al. 2002. SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7. Molecular Pharmacology 62: 65–74.

    Article  CAS  PubMed  Google Scholar 

  16. Lee, H.H., E.H. Meyer, S. Goya, M. Pichavant, H.Y. Kim, X. Bu, et al. 2010. Apoptotic cells activate NKT cells through T cell Ig-like mucin-like-1 resulting in airway hyperreactivity. Journal of Immunology 185: 5225–5235.

    Article  CAS  Google Scholar 

  17. Pichavant M, Goya S, Hamelmann E, Gelfand EW, Umetsu DT. Animal models of airway sensitization. Current Protocols in Immunology 2007; Chapter 15:Unit 15 18.

Download references

Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (81100018) and The Young Scientist Grant of Shanghai Health Bureau (2010Y039).

Conflict of Interest

The authors have declared that no competing interests exist.

Author information

Authors and Affiliations

  1. Department of Respiratory, Shanghai 10th People’s Hospital—Tongji University School of Medicine, 301 Middle Yanchang Rd, Shanghai, 200072, China

    Xiaolian Song, Shuanshuan Xie, Kun Lu & Changhui Wang

Authors
  1. Xiaolian Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuanshuan Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kun Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Changhui Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaolian Song.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Song, X., Xie, S., Lu, K. et al. Mesenchymal Stem Cells Alleviate Experimental Asthma by Inducing Polarization of Alveolar Macrophages. Inflammation 38, 485–492 (2015). https://doi.org/10.1007/s10753-014-9954-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-014-9954-6

KEY WORDS

Search

Navigation