Open Access

Response to 'Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4' - authors' reply

  • Dong Hyun Sohn1, 2,
  • Jeremy Sokolove1, 2,
  • Orr Sharpe1, 2,
  • Jennifer C Erhart3, 4,
  • Piyanka E Chandra1, 2,
  • Lauren J Lahey1, 2,
  • Tamsin M Lindstrom1, 2,
  • Inyong Hwang1, 2,
  • Katherine A Boyer3, 4,
  • Thomas P Andriacchi3, 4 and
  • William H Robinson1, 2Email author
Contributed equally
Arthritis Research & Therapy201214:406

DOI: 10.1186/ar3892

Published: 12 September 2012

We thank Oliviero and colleagues for their interest in our recent publication [1] and for reporting their very interesting related experiments [2]. Their results strongly support the concept that extravascular plasma proteins may act as damage-associated molecular patterns, and specifically as Toll-like receptor 4 agonists. In addition, we note that the NALP-3 inflammasome exhibits dependence on Toll-like receptor 4 or other mechanisms of priming of IL-1β transcription, thereby generating pro-IL-1β that can be converted to IL-1β by the activated inflammasome [3].

Although biochemical measurement of plasma and serum were not performed, we suspect the enhanced effect of serum compared with plasma could be related to mediators generated in the clotting process or released by platelets during the clotting process (but not released in the generation of plasma) and not related to the removal of fibrinogen. The observation that fibrinogen is itself able to prime the response to calcium crystal-induced inflammation further supports the role of fibrinogen as a Toll-like receptor 4 agonist [4, 5], as demonstrated by its ability to prime the inflammasome for response to activation by calcium crystals.

We thank Oliviero and colleagues for sharing their results and look forward to future studies elucidating the potentially critical role of plasma proteins as extra-vascular damage-associated molecular patterns.

Notes

Abbreviations

IL: 

interleukin.

Declarations

Authors’ Affiliations

(1)
GRECC, VA Palo Alto Health Care System
(2)
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine
(3)
Bone and Joint Center, VA Palo Alto Health Care System
(4)
Department of Mechanical Engineering, Stanford University

References

  1. Sohn DH, Sokolove J, Sharpe O, Erhart JC, Chandra PE, Lahey LJ, Lindstrom TM, Hwang I, Boyer KA, Andriacchi TP, Robinson WH: Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4. Arthritis Res Ther. 2012, 14: R7-10.1186/ar3555.PubMed CentralView ArticlePubMed
  2. Oliviero F, Scanu A, Dayer J-M, Fiocco U, Sfriso P, Punzi L: Response to 'Plasma proteins present in osteoarthritic synovial fluid can stimulate cytokine production via Toll-like receptor 4'. Arthritis Res Ther. 2012, 14: 405-PubMed CentralView ArticlePubMed
  3. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J: Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006, 440: 237-241. 10.1038/nature04516.View ArticlePubMed
  4. Smiley ST, King JA, Hancock WW: Fibrinogen stimulates macrophage chemokine secretion through Toll-like receptor 4. J Immunol. 2001, 167: 2887-2894.View ArticlePubMed
  5. Sokolove J, Zhao X, Chandra PE, Robinson WH: Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcγ receptor. Arthritis Rheum. 2011, 63: 53-62.PubMed CentralView ArticlePubMed

Copyright

© BioMed Central Ltd 2012

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