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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Main Authors: Sofia Mogren, Frida Berlin, Lykke Eskilsson, Nicole Van Der Burg, Ellen Tufvesson, Cecilia K. Andersson
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/18/2916
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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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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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