Bonella F, Sixt S U, Thomassen J, Schmidt M, Cai M, Mori T, Guzman J, Costabel U
Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany.
Department of Anesthesiology, University Hospital, Düsseldorf, Germany.
Immunobiology. 2015 Mar;220(3):382-8. doi: 10.1016/j.imbio.2014.10.010. Epub 2014 Oct 23.
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.
肺泡蛋白沉积症（PAP）的特征是肺泡表面活性物质脂蛋白的蓄积。蛋白酶体参与非溶酶体蛋白降解。我们推测，PAP患者肺泡腔内具有酶活性的蛋白酶体增加。
研究了31例PAP患者（29例原发性，2例继发性）、14例疾病对照者（10例慢性阻塞性肺疾病患者和4例肺气肿患者）和18例健康对照者。通过酶联免疫吸附测定法（ELISA）检测支气管肺泡灌洗液（BALF）和血清中的20S蛋白酶体。通过荧光底物切割测定细胞外蛋白酶体的酶活性（pkat/mg）。
PAP患者BAL中的蛋白酶体浓度高于疾病对照者或健康受试者（分别为566±420 vs 53±27 vs 60±42ng/ml，两者均p<0.0001）。PAP患者的血清蛋白酶体水平高于健康对照者（825±712 vs 405±176ng/ml，p=0.018）。处于疾病活动期的PAP患者血清水平高于病情缓解者（1317±1176 vs 439±422ng/ml，p=0.008）。PAP患者BAL中的蛋白酶体酶活性增加（p<0.05）。
PAP患者BAL中的20S蛋白酶体增加且具有活性。细胞外蛋白酶体可能有助于PAP中蓄积蛋白的肺泡内降解。
