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Cited by 233Mast cells and histamineAsthma and respiratory diseasesProtease and Inhibitor Mechanisms

Human Mast Cells Release Metalloproteinase-9 on Contact with Activated T Cells: Juxtacrine Regulation by TNF-α

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Baram, Dana, Vaday, Gayle G, Salamon, Pazit, Drucker, Ilana, Hershkoviz, Rami, Mekori, Yoseph A·2001·The Journal of Immunology
DOI 10.4049/jimmunol.167.7.4008
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Abstract

Mast cells, essential effector cells in allergic inflammation, have been found to be activated in T cell-mediated inflammatory processes in accordance with their residence in close physical proximity to T cells. We have recently reported that mast cells release granule-associated mediators and TNF-alpha upon direct contact with activated T cells. This data suggested an unrecognized activation pathway, where mast cells may be activated during T cell-mediated inflammation. Herein, we show that this cell-cell contact results in the release of matrix metalloproteinase (MMP)-9 and the MMP inhibitor tissue inhibitor of metalloproteinase 1 from HMC-1 human mast cells or from mature peripheral blood-derived human mast cells. The expression and release of these mediators, as well as of beta-hexosaminidase and several cytokines, were also induced when mast cells were incubated with cell membranes isolated from activated, but not resting, T cells. Subcellular fractionation revealed that the mature form of MMP-9 cofractionated with histamine and tryptase, indicating its localization within the secretory granules. MMP-9 release was first detected at 6 h and peaked at 22 h of incubation with activated T cell membranes, while TNF-alpha release peaked after only 6 h. Anti-TNF-alpha mAb inhibited the T cell membrane-induced MMP-9 release, indicating a possible autocrine regulation of MMP release by mast cell TNF-alpha. This cascade of events, whereby mast cells are activated by T cells to release cytokines and MMP-9, which are known to be essential for leukocyte extravasation and recruitment to affected sites, points to an important immunoregulatory function of mast cells within the context of T cell-mediated inflammatory processes.

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Authors
Baram, D., Vaday, G. G., Salamon, P., Drucker, I., Hershkoviz, R., & Mekori, Y. A.
Affiliations
  • Meir Medical Center (IL)
  • Weizmann Institute of Science (IL)
  • Tel Aviv University (IL)
ORCID
Mekori, Yoseph A
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2001-10-01
Volume
167
Issue
7
Pages
4008-4016
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.167.7.4008
OpenAlex
W2104195884
Cited by
233
References
49
Citations by year
2026: 1 · 2025: 7 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 11 · 2020: 10 · 2019: 13 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 10 · 2014: 6 · 2013: 9 · 2012: 15
FWCI
3.34
Type
journal article
Language
en
Open access
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Israel Academy of Sciences and Humanities
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
mast cells, MMP-9, TIMP-1, TNF-α, T cell-mediated inflammation, juxtacrine signaling, cell-cell contact, mast cell activation, secretory granules, leukocyte transmigration, immune regulation, HMC-1 cells
MeSH terms
Antibodies, Monoclonal, beta-N-Acetylhexosaminidases, Cells, Cultured, Enzyme Precursors, Humans, Lymphocyte Activation, Mast Cells, RNA, Messenger, T-Lymphocytes, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha, Cytokines, Collagenases, Models, Immunological, Jurkat Cells, Tissue Inhibitor of Metalloproteinase-1, Autocrine Communication, Matrix Metalloproteinase 9, Secretory Vesicles

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