Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells
Tissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor...
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MDPI AG
2022-09-01
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author | Sofia Mogren Frida Berlin Lykke Eskilsson Nicole Van Der Burg Ellen Tufvesson Cecilia K. Andersson |
author_facet | Sofia Mogren Frida Berlin Lykke Eskilsson Nicole Van Der Burg Ellen Tufvesson Cecilia K. Andersson |
author_sort | Sofia Mogren |
collection | DOAJ |
description | Tissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor, urokinase plasminogen activator receptor (uPAR), has been shown to regulate bronchial epithelial repair responses. However, the impact of MC tryptase and chymase on functional properties and expression of uPAR in alveolar epithelial cells have not been fully investigated. Alveolar epithelial cell migration and wound healing were investigated using holographic live cell imaging of A549 cells in a wound scratch model post stimulation with tryptase or chymase. The expression of uPAR was investigated on the protein and gene level from cellular supernatants and in bronchoalveolar lavage fluid fractions from allergic asthmatics. We found that tryptase improved wound healing capacity, cellular migration and membrane bound uPAR expression. Chymase reduced gap closure capacity, cellular migration and membrane bound uPAR expression but increased soluble uPAR release. Our data suggest a dual regulatory response from the MC proteases in events related to uPAR expression and wound healing which could be important features in asthmatic disease. |
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issn | 2073-4409 |
language | English |
last_indexed | 2024-03-10T00:25:56Z |
publishDate | 2022-09-01 |
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spelling | doaj.art-b0f66339118140e591d3838bdd26deb42023-11-23T15:34:23ZengMDPI AGCells2073-44092022-09-011118291610.3390/cells11182916Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial CellsSofia Mogren0Frida Berlin1Lykke Eskilsson2Nicole Van Der Burg3Ellen Tufvesson4Cecilia K. Andersson5Department of Experimental Medical Science, BMC, Lund University, 222 42 Lund, SwedenDepartment of Experimental Medical Science, BMC, Lund University, 222 42 Lund, SwedenDepartment of Experimental Medical Science, BMC, Lund University, 222 42 Lund, SwedenDepartment of Clinical Sciences, BMC, Lund University, 222 42 Lund, SwedenDepartment of Clinical Sciences, BMC, Lund University, 222 42 Lund, SwedenDepartment of Experimental Medical Science, BMC, Lund University, 222 42 Lund, SwedenTissue damage, epithelial alterations, and intraepithelial presence of mast cells (MCs) are characteristics of asthma pathogenesis. Increased alveolar infiltration of MC populations has also been identified as a feature of asthma and other chronic respiratory diseases. The asthma associated receptor, urokinase plasminogen activator receptor (uPAR), has been shown to regulate bronchial epithelial repair responses. However, the impact of MC tryptase and chymase on functional properties and expression of uPAR in alveolar epithelial cells have not been fully investigated. Alveolar epithelial cell migration and wound healing were investigated using holographic live cell imaging of A549 cells in a wound scratch model post stimulation with tryptase or chymase. The expression of uPAR was investigated on the protein and gene level from cellular supernatants and in bronchoalveolar lavage fluid fractions from allergic asthmatics. We found that tryptase improved wound healing capacity, cellular migration and membrane bound uPAR expression. Chymase reduced gap closure capacity, cellular migration and membrane bound uPAR expression but increased soluble uPAR release. Our data suggest a dual regulatory response from the MC proteases in events related to uPAR expression and wound healing which could be important features in asthmatic disease.https://www.mdpi.com/2073-4409/11/18/2916mast celltryptasechymasealveolar epithelial cellswound healingmigration |
spellingShingle | Sofia Mogren Frida Berlin Lykke Eskilsson Nicole Van Der Burg Ellen Tufvesson Cecilia K. Andersson Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells Cells mast cell tryptase chymase alveolar epithelial cells wound healing migration |
title | Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells |
title_full | Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells |
title_fullStr | Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells |
title_full_unstemmed | Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells |
title_short | Mast Cell Proteases Promote Diverse Effects on the Plasminogen Activation System and Wound Healing in A549 Alveolar Epithelial Cells |
title_sort | mast cell proteases promote diverse effects on the plasminogen activation system and wound healing in a549 alveolar epithelial cells |
topic | mast cell tryptase chymase alveolar epithelial cells wound healing migration |
url | https://www.mdpi.com/2073-4409/11/18/2916 |
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