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Caveolin-initiated macropinocytosis is required for efficient silica nanoparticles' transcytosis across the alveolar epithelial barrier.
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.
Afiliação
  • Detampel P; Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada.
  • Tehranian S; Division of Pharmaceutical Technology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
  • Mukherjee P; Department of Chemical and Petroleum Engineering, University of Calgary, Calgary, AB, Canada.
  • Foret M; Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada.
  • Fuerstenhaupt T; Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada.
  • Darbandi A; Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada.
  • Bogari N; Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada.
  • Hlasny M; Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada.
  • Jeje A; Department of Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada.
  • Olszewski MA; Department of Chemical and Petroleum Engineering, University of Calgary, Calgary, AB, Canada.
  • Ganguly A; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
  • Amrein M; Research Service, LTC Charles S. Kettles VA Medical Center, Ann Arbor, MI, USA.
Sci Rep ; 12(1): 9474, 2022 06 08.
Article em En | MEDLINE | ID: mdl-35676405
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dióxido de Silício / Nanopartículas Idioma: En Revista: Sci Rep Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dióxido de Silício / Nanopartículas Idioma: En Revista: Sci Rep Ano de publicação: 2022 Tipo de documento: Article