title: Human alveolar epithelial cells expressing tight junctions to model the air-blood barrier.
abstract: This paper describes a new human alveolar epithelial cell line (hAELVi - human Alveolar Epithelial Lentivirus immortalized) with type I-like characteristics and functional tight junctions, suitable to model the air-blood barrier of the peripheral lung. Primary human alveolar epithelial cells were immortalized by a novel regimen, grown as monolayers on permeable filter supports and characterized morphologically, biochemically and biophysically. hAELVi cells maintain the capacity to form tight intercellular junctions, with high trans-epithelial electrical resistance (> 1000 Ω*cm²). The cells could be kept in culture over several days, up to passage 75, under liquid-liquid as well as air-liquid conditions. Ultrastructural analysis and real time PCR revealed type I-like cell properties, such as the presence of caveolae, expression of caveolin-1, and absence of surfactant protein C. Accounting for the barrier properties, inter-digitations sealed with tight junctions and desmosomes were also observed. Low permeability of the hydrophilic marker sodium fluorescein confirmed the suitability of hAELVi cells for in vitro transport studies across the alveolar epithelium. These results suggest that hAELVi cells reflect the essential features of the air-blood barrier, as needed for an alternative to animal testing to study absorption and toxicity of inhaled drugs, chemicals and nanomaterials.
authors.affiliation: Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Kuehn
authors.affiliation: Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kletting
authors.affiliation: Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany.
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Souza Carvalho-Wodarz
authors.affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Urska
authors.initials: U
authors.lastname: Repnik
authors.affiliation: Department of Biosciences, University of Oslo, Oslo, Norway.
authors.forename: Gareth
authors.initials: G
authors.lastname: Griffiths
authors.affiliation: Saarland University, Institute of Human Genetics, University Hospital, Homburg/Saar, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Fischer
authors.affiliation: Saarland University, Institute of Human Genetics, University Hospital, Homburg/Saar, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Meese
authors.affiliation: SHG Clinics, Department of Cardiothoracic Surgery, Voelklingen Heart Center, Völklingen, Germany.
authors.forename: Hanno
authors.initials: H
authors.lastname: Huwer
authors.affiliation: Model Systems for Infection and Immunity, Helmholtz-Centre for Infection Research (HZI), Braunschweig, Germany.|Experimental Hematology, Medical School Hannover, Hannover, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wirth
authors.affiliation: InSCREENeX GmbH, Braunschweig, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: May
authors.affiliation: Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schneider-Daum
authors.affiliation: Drug Delivery (DDEL), Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany.|Department of Pharmacy, Saarland University, Saarbrücken, Germany.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D056809:Alveolar Epithelial Cells / Q000378:metabolism*; D015824:Blood-Air Barrier / Q000502:physiology*; D002460:Cell Line; D017097:Electric Impedance; D006801:Humans; D019108:Tight Junctions / Q000502:physiology*
keywords: ATI cells; Lentivirus immortalization; inhalation toxicology; pulmonary drug delivery