[6] Tryptase: A mast cell serine protease

Schwartz, Lawrence B.

doi:10.1016/0076-6879(94)44008-5

Cited by 83 publications

(56 citation statements)

References 58 publications

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“…The mouse 3T3 fibroblast cell line was obtained from American Type Tissue Culture (Rockville, MD). Heparin proteoglycan ( ‫ف‬ 750,000 D) from rat peritoneal mast cells (25) and porcine heparin glycosaminoglycan (1,,000 D) (Sigma Chemical Co.) (26) were prepared as described. Gly-Phe-CHN 2 , a DPPI-specific inhibitor, was prepared as described (16) and kindly provided by Dr. W. Serafin (Vanderbilt University, Nashville, TN).…”

Section: Methodsmentioning

confidence: 99%

“…mRNAs corresponding to both ␣ -and ␤ -tryptase encode proteins that are 92% identical and are found in almost all preparations of mast cells dispersed from human lung and skin (9). Using immunoassays that distinguish recombinant human (rh) 1 ␣ -and ␤ -tryptase from one another, ␣ -tryptase is the predominant form of tryptase detected in normal serum and is markedly elevated in patients with systemic mastocytosis, whereas ␤ -tryptase is the major form elevated in serum during systemic anaphylaxis (10). A molecular explanation for the apparent constitutive secretion of ␣ -tryptase, and secretory granule storage of ␤ -tryptase, as yet, is lacking.…”

Section: Introductionmentioning

confidence: 99%

“…Tryptase, a neutral serine protease, is the most abundant protein component of human mast cells, where it is selectively stored with full enzymatic activity in the secretory granules of all types of human mast cells, the major effector cell of allergic reactions (1). When activated mast cells degranulate, they release histamine and tryptase in parallel (2).…”

Section: Introductionmentioning

confidence: 99%

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A novel heparin-dependent processing pathway for human tryptase. Autocatalysis followed by activation with dipeptidyl peptidase I.

Sakai

Ren²,

Schwartz³

1996

J. Clin. Invest.

144

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Tryptase is the major protein constituent of human mast cells, where it is stored within the secretory granules as a fully active tetramer. Two tryptase genes ( ␣ and ␤ ) are expressed by human mast cells at the level of mRNA and protein, each with a 30 amino acid leader sequence. Recombinant precursor forms of human ␣ -and ␤ -tryptase were produced in a baculovirus system, purified, and used to study their processing. Monomeric ␤ -protryptase first is shown to be intermolecularly autoprocessed to monomeric ␤ -pro'tryptase at acid pH in the presence of heparin by cleavage between Arg Ϫ 3 and Val Ϫ 2 in the leader peptide. The precursor of ␣ -tryptase has an Arg Ϫ 3 to Gln Ϫ 3 mutation that precludes autoprocessing. This may explain why ␣ -tryptase is not stored in secretory granules, but instead is constitutively secreted by mast cells and is the predominant form of tryptase found in blood in both healthy subjects and those with systemic mastocytosis under nonacute conditions. Second, the NH 2 -terminal activation dipeptide on ␤ -pro'tryptase is removed by dipeptidyl peptidase I at acid pH in the absence of heparin to yield an inactive monomeric form of tryptase. Conversion of the catalytic portion of ␤ -tryptase to the active homotetramer at acid pH requires heparin. Thus, ␤ -tryptase homotetramers probably account for active enzyme detected in vivo. Also, processing of tryptase to an active form should occur optimally only in cells that coexpress heparin proteoglycan, restricting this pathway to a mast cell lineage. ( J. Clin. Invest. 1996. 97: 988-995.)

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A novel heparin-dependent processing pathway for human tryptase. Autocatalysis followed by activation with dipeptidyl peptidase I.

Sakai

Ren²,

Schwartz³

1996

J. Clin. Invest.

144

View full text Add to dashboard Cite

show abstract

“…Additional studies, intended to delineate the responsible mast cell mediator, disclosed that the serine endopeptidase tryptase (10) was largely responsible for the angiogenic effect. This tetrameric enzyme is released in abundant quantity from mast cells that are ionically bound to heparin proteoglycan, which stabilizes tryptase in its enzymatically active form (11). Although two genes for human tryptase have been identified, ␤ -tryptase appears to account for the enzymatically active enyme found in human lung mast cells and the mast cell leukemia cell line HMC-1 (12,13).…”

Section: Introductionmentioning

confidence: 99%

Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor.

Blair¹,

Meng²,

Marchese³

et al. 1997

J. Clin. Invest.

392

279

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“…20,23 These enzymes serve as specific markers for mast cells. 24 Chymase can directly degrade components of the basement membrane, including collagen types IV and V, laminin, fibronectin, and elastin. 25 Tryptase can degrade pericellular matrix proteins such as fibronectin.…”

mentioning

confidence: 99%

Activation of Matrix-Degrading Metalloproteinases by Mast Cell Proteases in Atherosclerotic Plaques

Johnson

Jackson

Angelini

et al. 1998

ATVB

240

150

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Abstract-Recent studies suggest that mast cell-derived neutral proteases can activate matrix-degrading metalloproteinases (MMPs). We have investigated the role of the mast cell proteases tryptase and chymase in the activation of MMPs in human carotid endarterectomy specimens (atherosclerotic, nϭ32) and postmortem carotid arteries (control, nϭ17). In vitro degranulation of mast cells in atherosclerotic carotid arteries by compound 48/80 caused a significant increase in MMP activity. Addition of the nonselective tryptase inhibitor antipain, the specific trypsinlike protease inhibitor 4-amidinophenylmethanesulfonyl fluoride, and the chymase inhibitor chymostatin reduced this increase in MMP activity by 30Ϯ6%, 23Ϯ6%, and 9Ϯ2%, respectively. Immunocytochemistry identified significantly higher numbers of tryptase-containing cells (mast cells) and cells expressing MMP-1 and MMP-3 in the "shoulder" regions of atherosclerotic artery lesions compared with the tunica media of control arteries. Dual immunocytochemistry showed collocation of MMP-1 and MMP-3 with mast cells in the shoulder regions. Degranulation was observed in 78Ϯ5% (meanϮSEM) of mast cells in this area, whereas nonactivated mast cells were observed in all other areas. In situ zymography revealed caseinolytic and gelatinolytic activity in these areas. In conclusion, in vitro mast cell degranulation, which releases mast cell proteases, in carotid arteries increases MMP activity. Furthermore, elevated MMP-1 and MMP-3 expression is collocated with increased numbers of degranulated mast cells and with greater MMP activity in the shoulder regions of atherosclerotic plaques. Activation of MMPs by mast cell-derived proteases may be an important mechanism in atherosclerotic plaque destabilization. (Arterioscler Thromb Vasc Biol. 1998;18:1707-1715.)

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[6] Tryptase: A mast cell serine protease

Cited by 83 publications

References 58 publications

A novel heparin-dependent processing pathway for human tryptase. Autocatalysis followed by activation with dipeptidyl peptidase I.

A novel heparin-dependent processing pathway for human tryptase. Autocatalysis followed by activation with dipeptidyl peptidase I.

Human mast cells stimulate vascular tube formation. Tryptase is a novel, potent angiogenic factor.

Activation of Matrix-Degrading Metalloproteinases by Mast Cell Proteases in Atherosclerotic Plaques

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