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Mast Cells and the Rheumatoid Lesion

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The distribution and activation of mast cells (MCs) in the rheumatoid lesion has been examined by tryptase immunolocalisation. MCs were observed in all specimens examined, but their distribution and local concentrations varied, both within and between specimens. MC activation was observed at sites of cartilage erosion and was associated with localised oedema and matrix disruption [1]. Dual immunolocalisation studies often demonstrated co-distributions of MCs with the matrix metalloproteinases (MMPs) collagenase 1 and stromelysin 1, as well as the proinflammatory cytokines TNFα and IL-1β [2]. Although IL-15 is purported to induce TNFα and IL-1β expression by cells in vitro [3,4], its production in situ was not associated with MC activation, as judged by IHC.

The potent mediators of MCs, especially histamine, heparin, and TNFα, are all likely to modify the phenotype of both synoviocytes and chondrocytes. The addition of soluble MC products to synovial fibroblast cultures was shown not only to stimulate MMP production but also to activate the MMP precursors via processing by the MC serine proteinases tryptase and chymase [5]. Experiments using rheumatoid synovial explants and MC secretagogue, rabbit antibody to human IgE, have shown that MC activation induced tryptase release, increased PGE2 production, and brought about changes in both MMP [6] and cytokine production. Subsequent experiments have assessed the effects of added histamine or heparin on enzymically dissociated rheumatoid synovial cell cultures with respect to cytokine production. Collectively, the data demonstrate that MC activation in the rheumatoid lesion modulates MMP and proinflammatory cytokine expression by neighbouring cells, thereby suggesting an important contributory role in mediating matrix degradation and oedematous changes within microfoci of the rheumatoid lesion.

Work supported by the Arthritis Research Campaign, United Kingdom.

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Keywords

  • Tryptase
  • Proinflammatory Cytokine Expression
  • Rheumatoid Synovial Cell
  • Synovial Explants
  • Increase PGE2 Production