Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles’ transcytosis across the alveolar epithelial barrier
Abstract Removal of particulate materials that would otherwise cumulate within the airspace and hinder the gas exchange is one of the central processes of maintaining lung homeostasis. While the importance of the particle uptake by alveolar macrophages and their expulsion via the airways mucociliary...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-13388-7 |
| _version_ | 1817975356289712128 |
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| author | Pascal Detampel Sara Tehranian Priyanka Mukherjee Morgan Foret Tobias Fuerstenhaupt Ali Darbandi Nawaf Bogari Magda Hlasny Ayodeji Jeje Michal A. Olszewski Anutosh Ganguly Matthias Amrein |
| author_facet | Pascal Detampel Sara Tehranian Priyanka Mukherjee Morgan Foret Tobias Fuerstenhaupt Ali Darbandi Nawaf Bogari Magda Hlasny Ayodeji Jeje Michal A. Olszewski Anutosh Ganguly Matthias Amrein |
| author_sort | Pascal Detampel |
| collection | DOAJ |
| description | Abstract Removal of particulate materials that would otherwise cumulate within the airspace and hinder the gas exchange is one of the central processes of maintaining lung homeostasis. While the importance of the particle uptake by alveolar macrophages and their expulsion via the airways mucociliary escalator is well established, very little is known about the alternative route for removing the particles via direct crossing the lung epithelium for transfer into the pulmonary lymph and bloodstream. This study dissected sequential mechanisms involved in nanoparticle transcytosis through the alveolar epithelial cell layer. By a combination of live cell, super resolution, and electron microscopy and RNA interference study, we have dissected temporal steps of nanoparticle transcytosis through alveolar epithelium. Our study revealed that caveolin is essential for the firm adhesion of the silica nanoparticle agglomerates to the apical membrane and their subsequent rapid internalization with the help of macropinocytic elements C-terminal-binding protein1 and Rabankyrin-5 but not dynamin. Actin, but not microtubules, played a major role in nanoparticle uptake and subsequent transportation. The compartments with nanoparticles were tethered to trans-Golgi network to be jointly transported along actin stress fibers across the cytoplasm, employing a myosin-dependent mechanism. The trans-Golgi nanoparticle transport machinery was positive to Rab6A, a marker linked to vesicle exocytosis. Exocytosis was primarily occurring at the basolateral plane of the alveolar epithelial cells. The high-proficiency novel caveolin and Rabankyrin-5 associated uptake and transcellular transport of nanoparticles across the AEC barrier supports its importance in clearance of amorphous silica and other types of non-inflammatory nanoparticles that are rapidly removed from the lungs following their inhalation. |
| first_indexed | 2024-04-13T21:48:54Z |
| format | Article |
| id | doaj.art-2ea7377b932343d891a0ce9668a34244 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T21:48:54Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2ea7377b932343d891a0ce9668a342442022-12-22T02:28:28ZengNature PortfolioScientific Reports2045-23222022-06-0112111410.1038/s41598-022-13388-7Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles’ transcytosis across the alveolar epithelial barrierPascal Detampel0Sara Tehranian1Priyanka Mukherjee2Morgan Foret3Tobias Fuerstenhaupt4Ali Darbandi5Nawaf Bogari6Magda Hlasny7Ayodeji Jeje8Michal A. Olszewski9Anutosh Ganguly10Matthias Amrein11Department of Cell Biology and Anatomy, University of CalgaryDepartment of Chemical and Petroleum Engineering, University of CalgaryDepartment of Cell Biology and Anatomy, University of CalgaryDepartment of Cell Biology and Anatomy, University of CalgaryDepartment of Cell Biology and Anatomy, University of CalgaryDepartment of Cell Biology and Anatomy, University of CalgaryDepartment of Cell Biology and Anatomy, University of CalgaryDepartment of Cell Biology and Anatomy, University of CalgaryDepartment of Chemical and Petroleum Engineering, University of CalgaryDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health SystemDepartment of Cell Biology and Anatomy, University of CalgaryDepartment of Cell Biology and Anatomy, University of CalgaryAbstract Removal of particulate materials that would otherwise cumulate within the airspace and hinder the gas exchange is one of the central processes of maintaining lung homeostasis. While the importance of the particle uptake by alveolar macrophages and their expulsion via the airways mucociliary escalator is well established, very little is known about the alternative route for removing the particles via direct crossing the lung epithelium for transfer into the pulmonary lymph and bloodstream. This study dissected sequential mechanisms involved in nanoparticle transcytosis through the alveolar epithelial cell layer. By a combination of live cell, super resolution, and electron microscopy and RNA interference study, we have dissected temporal steps of nanoparticle transcytosis through alveolar epithelium. Our study revealed that caveolin is essential for the firm adhesion of the silica nanoparticle agglomerates to the apical membrane and their subsequent rapid internalization with the help of macropinocytic elements C-terminal-binding protein1 and Rabankyrin-5 but not dynamin. Actin, but not microtubules, played a major role in nanoparticle uptake and subsequent transportation. The compartments with nanoparticles were tethered to trans-Golgi network to be jointly transported along actin stress fibers across the cytoplasm, employing a myosin-dependent mechanism. The trans-Golgi nanoparticle transport machinery was positive to Rab6A, a marker linked to vesicle exocytosis. Exocytosis was primarily occurring at the basolateral plane of the alveolar epithelial cells. The high-proficiency novel caveolin and Rabankyrin-5 associated uptake and transcellular transport of nanoparticles across the AEC barrier supports its importance in clearance of amorphous silica and other types of non-inflammatory nanoparticles that are rapidly removed from the lungs following their inhalation.https://doi.org/10.1038/s41598-022-13388-7 |
| spellingShingle | Pascal Detampel Sara Tehranian Priyanka Mukherjee Morgan Foret Tobias Fuerstenhaupt Ali Darbandi Nawaf Bogari Magda Hlasny Ayodeji Jeje Michal A. Olszewski Anutosh Ganguly Matthias Amrein Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles’ transcytosis across the alveolar epithelial barrier Scientific Reports |
| title | Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles’ transcytosis across the alveolar epithelial barrier |
| title_full | Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles’ transcytosis across the alveolar epithelial barrier |
| title_fullStr | Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles’ transcytosis across the alveolar epithelial barrier |
| title_full_unstemmed | Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles’ transcytosis across the alveolar epithelial barrier |
| title_short | Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles’ transcytosis across the alveolar epithelial barrier |
| title_sort | caveolin initiated macropinocytosis is required for efficient silica nanoparticles transcytosis across the alveolar epithelial barrier |
| url | https://doi.org/10.1038/s41598-022-13388-7 |
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