Extracellular 20S proteasome in BAL and serum of patients with alveolar proteinosis

• Published in: Immunobiology (1979) Vol. 220; no. 3; pp. 382 - 388
• Main Authors: Bonella, F., Sixt, S.U., Thomassen, J., Schmidt, M., Cai, M., Mori, T., Guzman, J., Costabel, U.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.03.2015
• Subjects: Advanced Basic Science; Allergy and Immunology; Alveolar proteinosis; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid - chemistry; Emphysema - metabolism; Extracellular proteasome; Female; Humans; Lipoproteins - metabolism; Male; Middle Aged; Proteasome Endopeptidase Complex - blood; Proteasome Endopeptidase Complex - metabolism; Proteolysis; Pulmonary Alveolar Proteinosis - pathology; Pulmonary Alveoli - enzymology; Pulmonary Disease, Chronic Obstructive - metabolism; Extracellular proteasome; BALF; Alveolar proteinosis; TLC; VC; FVC; DLCO; GM-CSF; OD; TBB; Bronchoalveolar lavage; WLL; FEV1; HRCT; PAP; ELISA; PFT; transbronchial biopsy; forced vital capacity; diffusing capacity of the lung for carbon monoxide; granulocyte macrophage colony stimulating factor; vital capacity; pulmonary function tests; high resolution computed tomography; pulmonary alveolar proteinosis; forced expiratory volume in one second; whole lung lavage; total lung capacity; enzyme-linked immunosorbent assay; bronchoalveolar lavage fluid; optical density
• ISSN: 0171-2985; 1878-3279; 1878-3279
• DOI: 10.1016/j.imbio.2014.10.010

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. 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. 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). 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.