title: SFTA3, a novel protein of the lung: three-dimensional structure, characterisation and immune activation.
abstract: The lung constantly interacts with numerous pathogens. Thus, complex local immune defence mechanisms are essential to recognise and dispose of these intruders. This work describes the detection, characterisation and three-dimensional structure of a novel protein of the lung (surfactant-associated protein 3 (SFTA3/SP-H)) with putative immunological features. Bioinformatics, biochemical and immunological methods were combined to elucidate the structure and function of SFTA3. The tissue-specific detection and characterisation was performed by using electron microscopy as well as fluorescence imaging. Three-dimensional structure generation and analysis led to the development of specific antibodies and, as a consequence, to the localisation of a novel protein in human lung under consideration of cystic fibrosis, asthma and sepsis. In vitro experiments revealed that lipopolysaccharide induces expression of SFTA3 in the human lung alveolar type II cell line A549. By contrast, the inflammatory cytokines interleukin (IL)-1β and IL-23 inhibit expression of SFTA3 in A549. Sequence- and structure-based prediction analysis indicated that the novel protein is likely to belong to the family of lung surfactant proteins. The results suggest that SFTA3 is an immunoregulatory protein of the lung with relevant protective functions during inflammation at the mucosal sites.
authors.affiliation: Institute of Anatomy, Dept II, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany These two authors contributed equally to this work martin.schicht@anatomie2.med.uni-erlangen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Schicht
authors.affiliation: Institute of Anatomy, Dept II, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany These two authors contributed equally to this work.
authors.forename: Felix
authors.initials: F
authors.lastname: Rausch
authors.affiliation: Dept of Molecular Pneumology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Susetta
authors.initials: S
authors.lastname: Finotto
authors.affiliation: Dept of Molecular Pneumology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Mathews
authors.affiliation: Dept of Molecular Pneumology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Mattil
authors.affiliation: Dept of Molecular Pneumology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schubert
authors.affiliation: Dept of Molecular Pneumology, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Koch
authors.affiliation: Dept of Otorhinolaryngology, Head and Neck Surgery, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Traxdorf
authors.affiliation: Dept of Otorhinolaryngology, Head and Neck Surgery, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bohr
authors.affiliation: Dept of Hygiene of the Medical Faculty, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Worlitzsch
authors.affiliation: Dept of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Halle, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brandt
authors.affiliation: Institute of Anatomy, Dept II, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Garreis
authors.affiliation: Dept of Ophthalmology, Ruprecht-Karls University Heidelberg, Heidelberg, Germany.
authors.forename: Saadettin
authors.initials: S
authors.lastname: Sel
authors.affiliation: Institute of Anatomy, Dept II, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany These two authors contributed equally to this work.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Paulsen
authors.affiliation: Institute of Anatomy, Dept II, Friedrich Alexander University Erlangen-Nuremberg, Erlangen, Germany These two authors contributed equally to this work.
authors.forename: Lars
authors.initials: L
authors.lastname: Bräuer
mesh_terms: D045744:Cell Line, Tumor; D003550:Cystic Fibrosis / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007150:Immunohistochemistry; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009092:Mucous Membrane / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D053759:Interleukin-23; D008070:Lipopolysaccharides; D037661:Pulmonary Surfactant-Associated Proteins; C000597598:SFTA3 protein, human; D013501:Surface-Active Agents