Proteinase-activated receptor-2 (PAR2) mediates the pro-inflammatory effects of synovial mast cells.

H.S. Palmer, E.B. Kelso, J.C. Lockhart, C.P. Sommerhoff, R. Plevin, F.G. Goh, W.R. Ferrell

Research output: Contribution to journalArticlepeer-review


Mast cells are hypothesized to play a role in the pathogenesis of rheumatoid arthritis (RA) by mechanisms requiring elucidation. Tryptase released from these cells can activate protease-activated receptor 2 (PAR-2), which was recently shown to have proinflammatory actions. The purpose of this study was to examine the relationship between synovial mast cells and PAR-2. Mast cell proximity to PAR-2–expressing cells was investigated in RA synovium. In murine studies, we assessed the capacity of mast cell tryptase to mediate synovial proinflammatory responses via PAR-2 and whether degranulating mast cells induced synovial hyperemia by PAR-2 activation.
RA synovial tissue was examined by immunohistochemistry. PAR-2+/+ and PAR-2−/− C57BL/6J mice were used to investigate the PAR-2 dependence of compound 48/80–induced synovial hyperemia, as measured by laser Doppler imaging, and joint swelling and hyperemic responses to recombinant human β-tryptase.
Mast cells and synovial lining cells staining for PAR-2 were colocalized in RA articular tissue. Compound 48/80 administration resulted in vasodilatation in PAR-2+/+ mice but not in PAR-2−/− mice, which showed a vasoconstrictor response. Eliminating the 5-hydroxytryptamine–mediated component of this response with methysergide unveiled an enhanced PAR-2–mediated vasodilatation to compound 48/80 in PAR-2+/+ mice and ablated the vasoconstrictor response in PAR-2−/− mice. Treatment with β-tryptase resulted in dose-dependent knee joint swelling and synovial vasodilatation in PAR-2+/+ mice but not PAR-2−/− mice.
This in vivo study is the first to explore the relationship between synovial mast cells and PAR-2. Our results support the hypothesis that mast cells contribute to the pathogenesis of inflammatory arthritis through PAR-2 activation via release of mast cell tryptase.
Original languageEnglish
Pages (from-to)3532-3540
Number of pages9
JournalArthritis & Rheumatology
Issue number11
Publication statusPublished - 2007


  • PAR2
  • rheumatoid arthritis
  • mast cells


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