F Bonella1, S U Sixt2, J Thomassen2, M Schmidt2, M Cai1, T Mori3, J Guzman4, U Costabel5. 1. Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany. 2. Department of Anesthesiology, University Hospital, Düsseldorf, Germany. 3. Radioisotope Research Centre, Nara Medical University School of Medicine, Kashihara, Japan. 4. General and Experimental Pathology, Ruhr-University, Bochum, Germany. 5. Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany. Electronic address: ulrich.costabel@ruhrlandklinik.uk-essen.de.
Abstract
BACKGROUND AND OBJECTIVES: 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. PATIENTS AND 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.
BACKGROUND AND OBJECTIVES: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. PATIENTS AND 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.