Cited by 318Mast cells and histamineAsthma and respiratory diseasesProtease and Inhibitor Mechanisms

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Mast cell tryptase stimulates the synthesis of type I collagen in human lung fibroblasts

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Cairns, J A, Walls, A F·1997·Journal of Clinical Investigation

DOI 10.1172/jci119290PMC PMC507947

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Abstract

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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Authors: Cairns, J. A., & Walls, A. F.
Affiliations: Southampton General Hospital (GB)
ORCID: Walls, A F
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1997-03-15
Volume: 99
Issue: 6
Pages: 1313-1321
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci119290
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 › Pulmonary and Respiratory Medicine › 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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Mast cell tryptase stimulates the synthesis of type I collagen in human lung fibroblasts

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