Characterization and functional studies of rheumatoid synovial mast cells: Activation by secretagogues, anti‐IgE, and a histamine‐releasing lymphokine

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IgG and IgM autoantibodies directed against IgE were determined in 95 serum samples from 67 patients with systemic lupus erythematosus, by an enzyme-linked immunosorbent assay. IgM anti-IgE autoantibodies were found in 18 patients (27%) and IgG anti-IgE autoantibodies were detected in 23 patients (34%). The specificity of the immunoassay was confirmed by the ability to inhibit binding with IgE myeloma, but not other immunoglobulin isotypes and the demonstration that the reactivity was directed to the Fc E fragment of IgE. The IgG fraction of certain sera with anti-IgE activity was capable of inducing histamine release from control basophils and cutaneous mast cells. Clinical associations with the presence of anti-IgE activity were sought by retrospective chart analysis of 61 patients. Significant correlation was found with articular involvement, lymphadenopathy, and anti-DNA antibodies (P < 0.05). Anti-IgE autoantibodies are observed in a significant number of patients with systemic lupus erythematosus and may contribute to the pathogenesis of the vascular and articular lesions characteristic of this disease.

Section: Discussionsupporting

confidence: 67%

Anti‐ige autoantibodies in systemic lupus erythematosus

Gruber

Kaufman

Marchese

et al. 1988

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“…The detection of free histamine in the rheumatoid joint (5) and the demonstration of anti-IgE-induced histamine release from synovial mast cells (6) indicate that these mast cells are immunologically competent. Because serine proteases derived from rat serosal mast cells (SMC) degrade fibronectin (7) and type JV collagen (8) and because tryptase derived from human mast cells activates the metalloproteinase stromelysin (9), the mast cell has been implicated in the catabolism of the extracellular matrix of cartilage in rheumatoid arthritis.…”

Section: Conclusion These Studies Indicate That a Complexmentioning

confidence: 99%

Serosal mast cells maintain their viability and promote the metabolism of cartilage proteoglycans when cocultured with chondrocytes

Stevens

Somerville

Sewell

et al. 1992

Objective. To determine the consequences of mast cell (MC)-chondrocyte interactions.Methods. Cocultured cells were analyzed histochemically, morphologically, biochemically, and functionally.Results. Cocultured MC adhered to the chondrocytes and remained viable. Chondrocytes cocultured with nonactivated MC produced more proteoglycans than did chondrocytes cultured alone, and these proteoglycans possessed an intact hyaluronic acid-binding region. In contrast, most of the proteoglycans produced by chondrocytes cocultured with activated MC were degraded. Conclusion. These studies indicate that a complexFrom Mast cells are often present in increased numbers at sites of active cartilage erosion in the joints of patients with rheumatoid arthritis (1-6). The detection of free histamine in the rheumatoid joint (5) and the demonstration of anti-IgE-induced histamine release from synovial mast cells (6) indicate that these mast cells are immunologically competent. Because serine proteases derived from rat serosal mast cells (SMC) degrade fibronectin (7) and type JV collagen (8) and because tryptase derived from human mast cells activates the metalloproteinase stromelysin (9), the mast cell has been implicated in the catabolism of the extracellular matrix of cartilage in rheumatoid arthritis. However, a precise understanding of the role of mast cells in this disease has been hindered by the presence of other types of inflammatory cells in the rheumatoid joint, the lack of an in vitro model system for studying the participation of mast cells in this disorder, and the uncertainty of the phenotype of the mast cells in the diseased tissue.The discovery that rat SMC can be maintained ex vivo for at least 30 days when cocultured with mouse 3T3 fibroblasts or with rat osteoblast-like cells, but not with mouse keratinocytes, mouse macrophages, or bovine endothelial cells (10,ll) suggests that mesenchymal cells may specifically promote the viability of the SMC-like population of mast cells. A complex reciprocal interaction occurs during coculture of mouse bone marrow-derived mast cells and 3T3 fibroblasts, in which the phenotype of the mast cell is dramatically altered histochemically, morpho-

“…Numerous cellular participants of innate and adaptive immunity contribute to the pronounced inflammatory processes seen in rheumatoid synovitis. Our group (1)(2)(3)(4) and many other investigators (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) have obtained data implicating a prominent involvement of mast cells (MCs) and their mediators in RA and some animal models of this autoimmune disorder. On a weight basis, tetramer-forming ␤ tryptases (15)(16)(17)(18)(19) are the most abundant proteins present in the secretory granules of human MCs.…”

mentioning

confidence: 99%

The mouse mast cell–restricted tetramer‐forming tryptases mouse mast cell protease 6 and mouse mast cell protease 7 are critical mediators in inflammatory arthritis

McNeil

Shin

Campbell

et al. 2008

Objective. Increased numbers of mast cells (MCs) that express ␤ tryptases bound to heparin have been detected in the synovium of patients with rheumatoid arthritis (RA). The corresponding tryptases in mice are mouse MC protease 6 (mMCP-6) and mMCP-7. Although MCs have been implicated in RA and some animal models of arthritis, no direct evidence for a MC-restricted tryptase in the pathogenesis of inflammatory arthritis has been shown. We created transgenic mice that lack heparin and different combinations of mMCP-6 and mMCP-7, to evaluate the roles of MCrestricted tryptase-heparin complexes in an experimental model of arthritis.Methods. The methylated bovine serum albumin/ interleukin-1␤ (mBSA/IL-1␤) experimental protocol was used to induce inflammatory monarthritis in different mouse strains. Mice were killed at the time of peak disease on day 7, and histochemical methods were used to assess joint pathology.Results. Arthritis was induced in the knee joints of mBSA/IL-1␤-treated mMCP-6 ؉ /mMCP-7 ؊ and mMCP-6 ؊ /mMCP-7 ؉ C57BL/6 mice, and numerous activated MCs that had exocytosed the contents of their secretory granules were observed in the diseased mice. In contrast, arthritis was markedly reduced in heparindeficient mice and in mMCP-6 ؊ /mMCP-7 ؊ C57BL/6 mice.Conclusion. MC-derived tryptase-heparin complexes play important roles in mBSA/IL-1␤-induced arthritis. Because mMCP-6 and mMCP-7 can compensate for each other in this disease model, the elimination of both tryptases is necessary to reveal the prominent roles of these serine proteases in joint inflammation and destruction. Our data suggest that the inhibition of MC-restricted tryptases could have therapeutic potential in the treatment of RA.Rheumatoid arthritis (RA) is an inflammatory disorder of synovial joints characterized by damage to articular structures due to chronic inflammation of the synovium. Numerous cellular participants of innate and adaptive immunity contribute to the pronounced inflammatory processes seen in rheumatoid synovitis. Our group (1-4) and many other investigators (5-14) have obtained data implicating a prominent involvement of mast cells (MCs) and their mediators in RA and some animal models of this autoimmune disorder. On a weight basis, tetramer-forming ␤ tryptases (15)(16)(17)(18)(19) are the most abundant proteins present in the secretory granules of human MCs. Three ␤ tryptase complementary DNAs (designated hTryptase ␤1, ␤2, and ␤3) have been cloned.