Skip to main content

Evaluation of Synovial Mast Cell Functions in Autoimmune Arthritis

  • Protocol
  • First Online:
Mast Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1220))

Abstract

Mast cells are innate immune effector cells that reside in the healthy synovial sublining and expand in number with inflammation. These cells can play an important role in initiation of arthritis, but much about their biology and importance remains obscure. This chapter reviews the use of animal models for the study of mast cells in arthritis, with a particular focus on the K/BxN serum transfer model. We discuss tissue preparation and histological analysis for the assessment of joint inflammation, injury, and the presence and phenotype of synovial mast cells, as well as the use of bone marrow-derived mast cell (BMMC) engraftment into W/Wv mice as a tool to isolate the role of mast cells in joint inflammation and injury.

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

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Castor W (1960) The microscopic structure of normal human synovial tissue. Arthritis Rheum 3:140–151

    Article  CAS  PubMed  Google Scholar 

  2. Nigrovic PA, Lee DM (2007) Synovial mast cells: role in acute and chronic arthritis. Immunol Rev 217:19–37

    Article  CAS  PubMed  Google Scholar 

  3. Crisp AJ, Chapman CM, Kirkham SE, Schiller AL, Krane SM (1984) Articular mastocytosis in rheumatoid arthritis. Arthritis Rheum 27(8):845–851

    Article  CAS  PubMed  Google Scholar 

  4. Monach PA, Benoist C, Mathis D (2004) The role of antibodies in mouse models of rheumatoid arthritis, and relevance to human disease. Adv Immunol 82:217–248

    Article  CAS  PubMed  Google Scholar 

  5. Kouskoff V, Korganow AS, Duchatelle V, Degott C, Benoist C, Mathis D (1996) Organ-specific disease provoked by systemic autoimmunity. Cell 87(5):811–822

    Article  CAS  PubMed  Google Scholar 

  6. Korganow AS, Ji H, Mangialaio S, Duchatelle V, Pelanda R, Martin T et al (1999) From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins. Immunity 10(4):451–461

    Article  CAS  PubMed  Google Scholar 

  7. Matsumoto I, Staub A, Benoist C, Mathis D (1999) Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme. Science 286(5445):1732–1735

    Article  CAS  PubMed  Google Scholar 

  8. Courtenay JS, Dallman MJ, Dayan AD, Martin A, Mosedale B (1980) Immunisation against heterologous type II collagen induces arthritis in mice. Nature 283(5748):666–668

    Article  CAS  PubMed  Google Scholar 

  9. Sakaguchi N, Takahashi T, Hata H, Nomura T, Tagami T, Yamazaki S et al (2003) Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature 426(6965):454–460

    Article  CAS  PubMed  Google Scholar 

  10. Maccioni M, Zeder-Lutz G, Huang H, Ebel C, Gerber P, Hergueux J et al (2002) Arthritogenic monoclonal antibodies from K/BxN mice. J Exp Med 195(8):1071–1077

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Nigrovic PA, Lee DM (2006) Immune complexes and innate immunity in rheumatoid arthritis. In: Firestein GS, Panayi GS, Wollheim FA (eds) Rheumatoid arthritis: new frontiers in pathogenesis and treatment, 2nd edn. Oxford University Press, Oxford, pp 135–156

    Google Scholar 

  12. Matsumoto I, Maccioni M, Lee DM, Maurice M, Simmons B, Brenner M et al (2002) How antibodies to a ubiquitous cytoplasmic enzyme may provoke joint-specific autoimmune disease. Nat Immunol 3(4):360–365

    Article  CAS  PubMed  Google Scholar 

  13. Shin K, Gurish MF, Friend DS, Pemberton AD, Thornton EM, Miller HR et al (2006) Lymphocyte-independent connective tissue mast cells populate murine synovium. Arthritis Rheum 54(9):2863–2871

    Article  CAS  PubMed  Google Scholar 

  14. Lee DM, Friend DS, Gurish MF, Benoist C, Mathis D, Brenner MB (2002) Mast cells: a cellular link between autoantibodies and inflammatory arthritis. Science 297(5587):1689–1692

    Article  CAS  PubMed  Google Scholar 

  15. Guma M, Kashiwakura J, Crain B, Kawakami Y, Beutler B, Firestein GS et al (2010) JNK1 controls mast cell degranulation and IL-1{beta} production in inflammatory arthritis. Proc Natl Acad Sci U S A 107(51):22122–22127

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Nigrovic PA, Binstadt BA, Monach PA, Johnsen A, Gurish M, Iwakura Y et al (2007) Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1. Proc Natl Acad Sci U S A 104(7):2325–2330

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Zhou JS, Xing W, Friend DS, Austen KF, Katz HR (2007) Mast cell deficiency in Kit(W-sh) mice does not impair antibody-mediated arthritis. J Exp Med 204(12):2797–2802

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Feyerabend TB, Weiser A, Tietz A, Stassen M, Harris N, Kopf M et al (2011) Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity. Immunity 35(5):832–844

    Article  CAS  PubMed  Google Scholar 

  19. Katz HR, Austen KF (2011) Mast cell deficiency, a game of kit and mouse. Immunity 35(5):668–670

    Article  CAS  PubMed  Google Scholar 

  20. Shin K, Nigrovic PA, Crish J, Boilard E, McNeil HP, Larabee KS et al (2009) Mast cells contribute to autoimmune inflammatory arthritis via their tryptase/heparin complexes. J Immunol 182(1):647–656

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Adachi R, Krilis SA, Nigrovic PA, Hamilton MJ, Chung K, Thakurdas SM et al (2012) Ras guanine nucleotide-releasing protein-4 (RasGRP4) involvement in experimental arthritis and colitis. J Biol Chem 287(24):20047–20055

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Wipke BT, Wang Z, Kim J, McCarthy TJ, Allen PM (2002) Dynamic visualization of a joint-specific autoimmune response through positron emission tomography. Nat Immunol 3(4):366–372

    Article  CAS  PubMed  Google Scholar 

  23. Binstadt BA, Patel PR, Alencar H, Nigrovic PA, Lee DM, Mahmood U et al (2006) Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol 7(3):284–292

    Article  CAS  PubMed  Google Scholar 

  24. Nigrovic PA, Malbec O, Lu B, Markiewski MM, Kepley C, Gerard N et al (2010) C5a receptor enables participation of mast cells in immune complex arthritis independently of Fcgamma receptor modulation. Arthritis Rheum 62(11):3322–3333

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Akilesh S, Petkova S, Sproule TJ, Shaffer DJ, Christianson GJ, Roopenian D (2004) The MHC class I-like Fc receptor promotes humorally mediated autoimmune disease. J Clin Invest 113(9):1328–1333

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Ohmura K, Johnsen A, Ortiz-Lopez A, Desany P, Roy M, Besse W et al (2005) Variation in IL-1{beta} gene expression is a major determinant of genetic differences in arthritis aggressivity in mice. Proc Natl Acad Sci U S A 102(35):12489–12494

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Wang J-X, King S, Bair A, Shnayder R, Hsieh Y-F, Shieh C-C et al (2012) Ly6G ligation blocks recruitment of neutrophils via a beta 2 integrin-dependent mechanism. Blood 120(7):1489–1498

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Gurish MF, Pear WS, Stevens RL, Scott ML, Sokol K, Ghildyal N et al (1995) Tissue-regulated differentiation and maturation of a v-abl-immortalized mast cell-committed progenitor. Immunity 3(2):175–186

    Article  CAS  PubMed  Google Scholar 

  29. Chen M et al (2006) Neutrophil-derived leukotriene B4 is required for inflammatory arthritis. J Exp Med 203:837–842

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Pettit AR et al (2001) TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis. Am J Pathol 159:1689–1699

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgements

This work was funded in part through the support of the Cogan Family Foundation (to P.A.N.). We are grateful to Dr. Altan Ercan for the K/BxN IgG ELISA protocol, to Ms. Theresa Bowman for histotechnical guidance, and to Dr. Nancy Kedersha for the immunofluorescence mounting medium protocols.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter A. Nigrovic M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Nigrovic, P.A., Shin, K. (2015). Evaluation of Synovial Mast Cell Functions in Autoimmune Arthritis. In: Hughes, M., McNagny, K. (eds) Mast Cells. Methods in Molecular Biology, vol 1220. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1568-2_26

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1568-2_26

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1567-5

  • Online ISBN: 978-1-4939-1568-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics