Alveolar and intraparenchymal proteasome in sarcoidosis

Abstract

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. To explore the role of proteasomes and immunoproteasomes in sarcoidosis. 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. 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 (101ng/ml±79; p=0.009) and III (119ng/ml±66; p=0.012), than in inactive sarcoidosis or in healthy controls (35ng/ml±34). In the absence of epoxomicin, all fluorogenic substrates were hydrolyzed by BAL supernatant of sarcoidosis patients and controls. 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.