title: Extracellular 20S proteasome in BAL and serum of patients with alveolar proteinosis.
abstract: OBJECTIVE
  Pulmonary alveolar proteinosis (PAP) is characterized by alveolar accumulation of surfactant lipoproteins. Proteasomes are involved in the nonlysosomal protein degradation. We hypothesize that enzymatically active proteasome is increased in the alveolar space of PAP.
  
  
  METHODS
  31 PAP patients (29 with primary, 2 with secondary form), 14 disease controls (10 with COPD and 4 with emphysema) and 18 healthy controls were studied. 20S Proteasome was measured by ELISA in bronchoalveolar lavage fluid (BALF) and in serum. Enzyme activity of extracellular proteasome (pkat/mg) was measured through fluorogenic substrate cleavage.
  
  
  RESULTS
  Proteasome concentration in BAL was higher in PAP patients than in disease controls or healthy subjects (566±420 vs 53±27 vs 60±42ng/ml, respectively, p<0.0001 for both). Serum proteasome levels were higher in PAP patients than in healthy controls (825±712 vs 405±176ng/ml, p=0.018). PAP patients with active disease had higher serum levels than those who achieved remission (1317±1176 vs 439±422ng/ml, p=0.008). Proteasomal enzyme activity was increased in BAL of PAP patients (p<0.05).
  
  
  CONCLUSIONS
  The 20S proteasome is increased and active in BAL of patients with PAP. Extracellular proteasome may contribute to the alveolar degradation of accumulated proteins in PAP.
authors.affiliation: Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Bonella
authors.affiliation: Department of Anesthesiology, University Hospital, Düsseldorf, Germany.
authors.forename: S U
authors.initials: SU
authors.lastname: Sixt
authors.affiliation: Department of Anesthesiology, University Hospital, Düsseldorf, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Thomassen
authors.affiliation: Department of Anesthesiology, University Hospital, Düsseldorf, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schmidt
authors.affiliation: Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Cai
authors.affiliation: Radioisotope Research Centre, Nara Medical University School of Medicine, Kashihara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.affiliation: General and Experimental Pathology, Ruhr-University, Bochum, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Guzman
authors.affiliation: Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany. Electronic address: ulrich.costabel@ruhrlandklinik.uk-essen.de.
authors.forename: U
authors.initials: U
authors.lastname: Costabel
mesh_terms: D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004646:Emphysema / Q000378:metabolism; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000097:blood* / Q000378:metabolism*; D059748:Proteolysis; D011649:Pulmonary Alveolar Proteinosis / Q000473:pathology*; D011650:Pulmonary Alveoli / Q000201:enzymology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism
chemical_list: D008074:Lipoproteins; D046988:Proteasome Endopeptidase Complex
keywords: Alveolar proteinosis; Bronchoalveolar lavage; Extracellular proteasome