Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation.

Gruber, Barry L.; Marchese, Mary J.; Suzuki, Ko; Schwartz, Lawrence B.; Okada, Yasunori; Nagase, Hideaki; Ramamurthy, N. S.

doi:10.1172/jci114344

Cited by 327 publications

(191 citation statements)

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“…Previous reports showed that mast cell extracts were capable of activating latent collagenase [ l l ] and mast cell tryptase of activating prostromelysin [12]. Here we report the effects of mast cell proteinases on four purified metalloproteinases, procollagenase (pMMP-l), progelatinase A (pMMP-2), prostromelysin (pMMP-3) and progelatinase B (pMMP-9).…”

mentioning

confidence: 73%

“…All the metalloproteinases are secreted as precursor forms requiring extracellular activation prior to substrate attack. Activation of the pro- Since mast cells are commonly associated with sites of connective-tissue lysis, for example at sites of tumour invasion in melanoma and breast carcinoma [7,81 and at cartilage erosion sites in rheumatoid arthritis [9], a potential role for this cell in matrix degradation has been proposed [7, 101. Previous reports showed that mast cell extracts were capable of activating latent collagenase [ l l ] and mast cell tryptase of activating prostromelysin [12]. Here we report the effects of mast cell proteinases on four purified metalloproteinases, procollagenase (pMMP-l), progelatinase A (pMMP-2), prostromelysin (pMMP-3) and progelatinase B (pMMP-9).…”

mentioning

confidence: 73%

“…This response might well be explained by the recent realisation that mast cells contain a variety of cytokines, including TNF a and IL-1 [40, 411, factors known to stimulate MMP expression by specific target cells. Activation of procollagenase (pMMP-1) by mast cell proteinases was first reported by Birkedal-Hansen et al, [ll], and subsequently tryptase was shown to be the effective component [42], albeit by its initial effect on pMMP-3 [12]. More recently both the active and the precursor forms of MMP-1 were reported to bind to mast cell granules [43], and although mast-cell-granule tryptase has limited natural substrates [44, 121 it was reported to process both pMMP-2 and fibronectin [45].…”

Section: Discussionmentioning

confidence: 99%

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Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B

Lees¹,

Taylor²,

Woolley³

1994

European Journal of Biochemistry

168

123

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Mast cell activation in vivo is often associated with areas of oedema and connective-tissue degradation. Tryptase and chymase are the major serine proteinases released by mast cells, but they appear to have little activity on most components of the extracellular matrix. The matrix metalloproteinases (MMP) are purported to degrade almost all connective tissue elements and are secreted by cells in the form of inactive precursors. Since the mechanisms of MMP activation in vivo are poorly understood we have examined the potential of mast cell proteinases to activate the precursor forms of human collagenase (MMP-l), stromelysin (MMP-3), gelatinase A (MMP-2) and gelatinase B (MMP-9).Mast cell proteinases prepared from purified dog mastocytoma cells were shown to process and activate purified precursor forms of both MMP-1 and MMP-3. Using antipain and chymostatin, inhibitors for tryptase and chymase, respectively, it was demonstrated that both pMMP-1 and pMMP-3 were effectively processed and activated by the chymase component. By contrast, tryptase activated only pMMP-3. The mast cell proteinases were unable to process or activate purified precursor forms of MMP-2 and MMP-9. However, MMP-3 previously activated by mast cell proteinases was shown to activate pMMP-9, but not pMMP-2. Since we have no evidence that mast cells express these four metalloenzymes, the release of mast cell serine proteinases following activatioddegranulation could contribute to local metalloproteinase activation and subsequent matrix degradation.Although numerous enzymes may contribute to the degradation of connective tissues, the family of metalloproteinases is of particular interest since they are purported to degrade almost all components of the extracellular matrix [l, 21. These enzymes are grouped into three main subclasses : interstitial [matrix metalloproteinase (MMP)-11 and polymorphonuclear (MMP-8) collagenases which degrade type I, I1 and I11 collagens; gelatinases A and B [MMP-2 (72 kDa) and MMP-9 (92 m a ) ] which degrade basement-membrane type IV collagen and gelatin; and stromelysins (MMP-3, MMP-10) with activity on a broad spectrum of substrates including proteoglycans, laminin, fibronectin and some collagen species [3]. While expressing different substrate specificities these metalloenzymes share some conserved sequence similarity and activation mechanisms [2]. All the metalloproteinases are secreted as precursor forms requiring extracellular activation prior to substrate attack. Activation of the pro- ~-enzymes has been demonstrated in vitro by proteolytic cleavage of their propeptide domains and also by organomercurial compounds such as aminophenyl mercuric acetate (H,NPhHgAc) [2, 4-61, but the activation mechanisms that function in vivo remain unclear.Since mast cells are commonly associated with sites of connective-tissue lysis, for example at sites of tumour invasion in melanoma and breast carcinoma [7, 81 and at cartilage erosion sites in rheumatoid arthritis [9], a potential role for this cell in matrix degradation has be...

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mentioning

confidence: 73%

mentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B

Lees¹,

Taylor²,

Woolley³

1994

European Journal of Biochemistry

168

123

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“…Nevertheless, our histochemical data also suggested greater loss of cartilage proteoglycans in the knee joints of mBSA/IL-1␤-treated mMCP-6 ϩ /mMCP-7 Ϫ C57BL/6 mice than similarly treated mMCP-6 Ϫ /mMCP-7 Ϫ C57BL/6 mice ( Figure 4). Al-though it is possible that MC-derived tryptases preferentially cleave aggrecan proteoglycans in cartilage in a direct manner, Gruber and coworkers (48,49) discovered that human ␤ tryptases can activate latent metalloproteinases, thereby also implicating indirect effects of these MC-restricted proteases on cartilage turnover. In support of the notion that tryptases have a role in extracellular matrix turnover, the MCs in the rat peritoneal cavity express the ortholog of mMCP-6 and hTryptase-␤1 (50), and we showed that the supernatants from activated rat peritoneal MCs can induce the rapid degradation of aggrecan proteoglycans in vitro (1).…”

Section: Mc-deficientmentioning

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

Arthritis & Rheumatism

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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.

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“…The activities of the mast cell serine proteases tryptase and chymase may directly contribute to matrix degradation: both proteases are reported to activate pro-MMP-3 and may therefore be important initiators of the MMP activation cascade leading to collagenase activation (Gruber et al, 1989;Lees, Taylor, & Woolley, 1994). Chymase is also reported to activate pro-MMP-1 directly (Lees et al, 1994;Saarinen, Kalkkinen, Welgus, & Kovanen, 1994).…”

Section: Synovium: Inflammation Hyperplasia Pannus Formation and Prmentioning

confidence: 99%

The role of proteases in pathologies of the synovial joint

Jones¹,

Riley²,

Buttle³

2008

The International Journal of Biochemistry & Cell Biology

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Synovial (diarthrodial) joints are employed within the body to provide skeletal mobility and have a characteristic structure adapted to provide a smooth almost frictionless surface for articulation. Pathologies of the synovial joint are an important cause of patient morbidity and can affect each of the constituent tissues. A common feature of these pathologies is degenerative changes in the structure of the tissue which is mediated, at least in part, by proteolytic activity. Most tissues of the synovial joint are composed primarily of extracellular matrix and key pathological roles in the degeneration of this matrix are performed by metalloproteinases such as matrix metallproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). However, other proteases such as cathepsin K are likely to play an important role, especially in bone turnover. In addition to the cleavage of structural proteins, proteolytic activities are employed to regulate the activity of other proteases, growth factors, cytokines and other inflammatory mediators. Proteases combine to form complex regulatory networks, the correct functioning of which is required for tissue homeostasis and the imbalance of which may be a feature of pathology. A precise understanding of the proteases involved in these networks is required for a true understanding of the associated pathology.

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Synovial procollagenase activation by human mast cell tryptase dependence upon matrix metalloproteinase 3 activation.

Cited by 327 publications

References 45 publications

Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B

Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B

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

The role of proteases in pathologies of the synovial joint

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