Matrix metalloproteinases in asthma: the role of mast cells and basophils
Matrix metalloproteinases in asthma: the role of mast cells and basophils
Matrix metalloproteinases (MMPs) have important roles in the migration of leukocytes between endothelial cells and through the tissue, matrix deposition and airway remodelling observed in asthma. Mast cells and basophils are major effector cells in asthma and, as they are known to migrate during this disorder, the release of MMPs from these cells was investigated. Both mast cells and basophils were found to contain significant amounts of both the gelatinases MMP 9 and the stromelysin MMP 3. Mast cells and basophils were also found to contain and release the physiological inhibitor of MMP 9 and MMP 3, tissue inhibitor of matrix metalloproteinases-1 (TIMP 1).
Leukocytes and lung cells were found to release MMP 9 and MMP 3 following challenge of basophils and mast cells respectively, with anti-IgE or A23187. Stimulation of lung cells and mixed leukocytes with concentrations of anti-IgE too low to induce measurable histamine release, resulted in the optimal liberation of MMPs. There was found to be cross-talk between basophils activated with low concentrations of anti-IgE and neutrophils, resulting in significant neutrophil MMP release. PAF was isolated as one of the candidate mediators of neutrophil-basophil cross-talk and was found to induce significant MMP release from neutrophils. Pure populations of mast cells and basophils released MMP 3 and MMP 9 on stimulation with both anti-IgE and A23187. Stimulation of cells with 0.1 μg/ml of anti-IgE resulted in the rapid liberation of stored MMPs from mast cells and basophils. Lower concentrations of anti-IgE (0.1 ng/ml) produced maximal MMP release after 5 hours, suggesting that small concentrations of anti-IgE promote the de novo synthesis inhibitor cyclohexamide.
University of Southampton
1999
Rich, Kirsty Leanne
(1999)
Matrix metalloproteinases in asthma: the role of mast cells and basophils.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Matrix metalloproteinases (MMPs) have important roles in the migration of leukocytes between endothelial cells and through the tissue, matrix deposition and airway remodelling observed in asthma. Mast cells and basophils are major effector cells in asthma and, as they are known to migrate during this disorder, the release of MMPs from these cells was investigated. Both mast cells and basophils were found to contain significant amounts of both the gelatinases MMP 9 and the stromelysin MMP 3. Mast cells and basophils were also found to contain and release the physiological inhibitor of MMP 9 and MMP 3, tissue inhibitor of matrix metalloproteinases-1 (TIMP 1).
Leukocytes and lung cells were found to release MMP 9 and MMP 3 following challenge of basophils and mast cells respectively, with anti-IgE or A23187. Stimulation of lung cells and mixed leukocytes with concentrations of anti-IgE too low to induce measurable histamine release, resulted in the optimal liberation of MMPs. There was found to be cross-talk between basophils activated with low concentrations of anti-IgE and neutrophils, resulting in significant neutrophil MMP release. PAF was isolated as one of the candidate mediators of neutrophil-basophil cross-talk and was found to induce significant MMP release from neutrophils. Pure populations of mast cells and basophils released MMP 3 and MMP 9 on stimulation with both anti-IgE and A23187. Stimulation of cells with 0.1 μg/ml of anti-IgE resulted in the rapid liberation of stored MMPs from mast cells and basophils. Lower concentrations of anti-IgE (0.1 ng/ml) produced maximal MMP release after 5 hours, suggesting that small concentrations of anti-IgE promote the de novo synthesis inhibitor cyclohexamide.
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Published date: 1999
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Local EPrints ID: 463606
URI: http://eprints.soton.ac.uk/id/eprint/463606
PURE UUID: f6aeca57-0611-4c1e-902a-9075060208c7
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Date deposited: 04 Jul 2022 20:54
Last modified: 04 Jul 2022 20:54
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Author:
Kirsty Leanne Rich
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