- Meeting abstract
- Open Access
Mast Cells and the Rheumatoid Lesion
© Current Science Ltd 2000
- Published: 15 November 1999
- Proinflammatory Cytokine Expression
- Rheumatoid Synovial Cell
- Synovial Explants
- Increase PGE2 Production
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 . 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 . 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 . 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  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.
- Tetlow LC, Woolley DE: Distribution, activation and tryptase/chymase phenotype of mast cells in the rheumatoid lesion. Ann Rheum Dis. 1995, 54: 549-555.PubMedPubMed CentralView ArticleGoogle Scholar
- Tetlow LC, Woolley DE: Mast cells, cytokines and metalloproteinases at the rheumatoid lesion: dual immunolocalisation studies. Ann Rheum Dis. 1995, 54: 896-903.PubMedPubMed CentralView ArticleGoogle Scholar
- McInnes IB, Leung BP, Sturrock RD, Field M, Liew FY: Interleukin-15 mediates T-cell dependent regulation of tumour necrosis factor-alpha production in rheumatoid arthritis. Nature Med. 1997, 3: 189-195. 10.1038/nm0297-189.PubMedView ArticleGoogle Scholar
- Sebbag M, Parry SL, Brennan FM, Feldmann M: Cytokine stimulation of T-lymphocytes regulates their capacity to induce monocyte production of tumour necrosis factor-alpha, but not interleukin-10: Possible relevance to pathophysiology of rheumatoid arthritis. Eur J Immunol. 1997, 27: 624-632.PubMedView ArticleGoogle Scholar
- Lees M, Taylor DJ, Woolley DE: Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinase A and B. Eur J Biochem. 1994, 223: 171-177. 10.1111/j.1432-1033.1994.tb18980.x.PubMedView ArticleGoogle Scholar
- Tetlow LC, Harper N, Dunningham T, Morris MA, Bertfield H, Woolley DE: Effects of induced mast cell activation on prostaglandin E and metalloproteinase production by rheumatoid synovial tissue in vivo. Ann Rheum Dis. 1998, 57: 25-32.PubMedPubMed CentralView ArticleGoogle Scholar