Mast cell tryptase stimulates the synthesis of type I collagen in human lung fibroblasts
Open accessAbstract
Mast cell activation is a characteristic feature of chronic inflammation, a condition that may lead to fibrosis as a result of increased collagen synthesis by fibroblasts. We have investigated the potential of tryptase, the major protease of human mast cells, to stimulate collagen synthesis in the human lung fibroblast cell line MRC-5. Tryptase was isolated from human lung tissue by ion-exchange and affinity chromatography. At concentrations of 18 and 36 mU/ml, tryptase stimulated both an increase in cell numbers, and a fivefold increase in DNA synthesis as determined by methyl-[3H]thymidine incorporation. Similar concentrations of tryptase resulted in a 2.5-fold increase in collagen synthesis as determined both by incorporation of [3H]proline into collagen, and by assay of hydroxyproline concentrations in the supernatants. There was also a twofold increase in collagenolytic activity in the culture medium after tryptase treatment, indicating that the increase in collagen synthesis was not a consequence of decreased collagenase production. All of these actions of tryptase were reduced in the presence of the protease inhibitors leupeptin and benzamidine hydrochloride, indicating a requirement for an active catalytic site. SDS-PAGE and autoradiographic analysis of the [3H]collagen produced by the cells revealed it to be predominantly type I collagen. Our findings suggest that the release of tryptase from activated mast cells may provide a signal for abnormal fibrosis in inflammatory disease.
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Mast cells produce tryptase, which stimulates fibroblast proliferation and collagen production.
“Mast cells also produce tryptase, a serine proteinase, which, remarkably, stimulates fibroblast proliferation and collagen production (142, 160, 161), and histamine, which also”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [161]
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- Authors
- Cairns, J. A., & Walls, A. F.
- Affiliations
- Southampton General Hospital (GB)
- ORCID
- Walls, A F
- Venue
- Journal of Clinical Investigation
- Published
- 1997-03-15
- Volume
- 99
- Issue
- 6
- Pages
- 1313-1321
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507947
- OpenAlex
- W2010465872
- Cited by
- 318
- References
- 60
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 9 · 2023: 10 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 10 · 2018: 10 · 2017: 3 · 2016: 5 · 2015: 9 · 2014: 8 · 2013: 12 · 2012: 7
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- tryptase, type I collagen synthesis, lung fibroblasts, pulmonary fibrosis, mast cell activation, chronic inflammation, protease inhibitors, collagenolytic activity, collagenase, MRC-5 cells, DNA synthesis
- MeSH terms
- Cell Division, Cell Line, Chromatography, Ion Exchange, Collagen, Fibroblasts, Humans, Hydroxyproline, Lung, Mast Cells, Proline, Serine Endopeptidases, Time Factors, Tritium, Tryptases, Chymases
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