Author:
Detampel Pascal,Tehranian Sara,Mukherjee Priyanka,Foret Morgan,Fuerstenhaupt Tobias,Darbandi Ali,Bogari Nawaf,Hlasny Magda,Jeje Ayodeji,Olszewski Michal A.,Ganguly Anutosh,Amrein Matthias
Abstract
AbstractRemoval 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.
Funder
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Nanotechnology scholarship from Alberta Ingenuity
VA Airborne Hazards and Burn Pits Center of Excellence
Canadian Institutes of Health Research
Publisher
Springer Science and Business Media LLC
Reference48 articles.
1. Vineis, P. & Fecht, D. Environment, cancer and inequalities—The urgent need for prevention. Eur. J. Cancer 103, 317–326 (2018).
2. Tegen, I. et al. Modelling soil dust aerosol in the Bodélé depression during the BoDEx campaign. Atmos. Chem. Phys. 6, 4345–4359 (2006).
3. Merget, R. et al. Health hazards due to the inhalation of amorphous silica. Arch. Toxicol. 75, 625–634 (2002).
4. U.S. EPA. Health Effects Of Inhaled Crystalline And Amorphous Silica. Health Effects Of Inhaled Crystalline And Amorphous Silica. https://cfpub.epa.gov/si/si_public_record_Report.cfm?Lab=NCEA&dirEntryId=12999 (2000).
5. Fruijtier-Pölloth, C. The toxicological mode of action and the safety of synthetic amorphous silica—A nanostructured material. Toxicology 294, 61–79 (2012).
Cited by
6 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献