title: Alveolar and intraparenchymal proteasome in sarcoidosis.
abstract: BACKGROUND
  In sarcoidosis, an antigen specific immune response is a putative mechanism, resulting in granulomatous inflammation. Since the proteasome is involved in antigen presentation, alterations in the alveolar and parenchymal proteasomal system may be a feature of sarcoidosis.
  
  
  OBJECTIVE
  To explore the role of proteasomes and immunoproteasomes in sarcoidosis.
  
  
  METHODS
  Total proteasome concentration and activity was assessed in bronchoalveolar lavage (BAL) supernatant obtained from sarcoidosis patients (n = 67) and healthy controls (n = 18) using ELISA and cleavage of specific fluorogenic substrates (±epoxomicin), respectively. Immunohistochemistry of lung tissue sections and immunocytochemistry of BAL macrophages for immunoproteasome was performed in sarcoidosis patients and controls.
  
  
  RESULTS
  Proteasome was present in BAL supernatants of all sarcoidosis patients. In sarcoidosis, abundant immunoproteasome staining was seen in pneumocytes type II and granulomas. Total proteasome concentration was greater in active sarcoidosis, stages II (101 ng/ml ± 79; p = 0.009) and III (119 ng/ml ± 66; p = 0.012), than in inactive sarcoidosis or in healthy controls (35 ng/ml ± 34). In the absence of epoxomicin, all fluorogenic substrates were hydrolyzed by BAL supernatant of sarcoidosis patients and controls.
  
  
  CONCLUSIONS
  Patients with active sarcoidosis but not healthy controls demonstrate immunoproteasome in the lung tissue and in granulomas. Thus, the putative immune response in sarcoidosis may be mediated or sustained by the proteasomal system.
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: S U
authors.initials: SU
authors.lastname: Sixt
authors.affiliation: Abteilung für Pneumologie und Allergologie, Ruhrlandklinik, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Costabel
authors.affiliation: Abteilung für Pneumologie und Allergologie, Ruhrlandklinik, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Bonella
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Grunert
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Alami
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Hakenbeck
authors.affiliation: Abteilung für Pneumologie und Allergologie, Ruhrlandklinik, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Bauer
authors.affiliation: Institut für Biochemie/CCM, Charité-Universitätsmedizin-Berlin, Berlin, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Dahlmann
authors.affiliation: Institut für Pathologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany.
authors.forename: K W
authors.initials: KW
authors.lastname: Schmid
authors.affiliation: Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Peters
authors.affiliation: Institut für Pathologie, Universitätsklinikum Essen, Universität Duisburg-Essen, Germany. Electronic address: jeremias.wohlschlaeger@uk-essen.de.
authors.forename: J
authors.initials: J
authors.lastname: Wohlschlaeger
mesh_terms: D000328:Adult; D000368:Aged; D056809:Alveolar Epithelial Cells / Q000201:enzymology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006099:Granuloma / Q000201:enzymology*; D006801:Humans; D016676:Macrophages, Alveolar / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000201:enzymology*; D017565:Sarcoidosis, Pulmonary / Q000201:enzymology*
chemical_list: D046988:Proteasome Endopeptidase Complex
keywords: Bronchoalveolar lavage; Circulating proteasome; Inflammation; Proteasome; Sarcoidosis