Pneumologie 2011; 65 - V283
DOI: 10.1055/s-0031-1271995

Up-regulated expression of immunoproteasome subunit LMP7 in alveolar macrophages of hypersensitivity pneumonitis

M Cai 1, S Sixt 2, F Bonella 3, T Anlasik 2, T Mori 4, J Guzman 5, U Costabel 6
  • 1Pneumology and Allergology, Ruhrlandklink Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital
  • 2Düsseldorf
  • 3Pneumology and Allergology, Ruhrlandklink Essen
  • 4Nara Medical University, Japan – Nara
  • 5General and Experimental Pathology, Ruhr University Bochum
  • 6Abteilung Pneumologie/Allergologie, Ruhrlandklinik Essen

Background: Proteasomes are important proteolytic complexes for the processing of endogenous antigen presentation by major histocompatibility complex (MHC) class I molecules. Low molecule weight protein (LMP) 2 and LMP7 are IFN-γ-inducible and MHC-II-encoded β subunits which can incorporate into the constitutive 20S proteasome and turn it to immunoproteasomes with alterations of catalytic properties.

Aim of the study: To compare the expressions of LMP2 and LMP7 in alveolar macrophages (AMs) of hypersensitivity pneumonitis (HP) and sarcoidosis.

Patients and Methods: BAL cells were collected from 24 granulomatous patients: 11 HP (8 acute/subacute, 3 chronic) and 13 sarcoidosis (9 inactive, 4 active), and 9 control subjects. Immunocytochemistry (ICC) was used to the cells with monoclonal antibodies against LMP2 and LMP7 (Biotrend Chemikalien GmbH, Koeln, Germany). Levels of LMP2 and LMP7 proteins were estimated by an intensity-associated score system.

Results: The positive rates and the scores of LMP7 expressed in AMs of HP patients were both markedly up-regulated compared with sarcoid patients (p<0.01) and controls (p<0.05), while the two indexes of LMP7 were similar between sarcoid patients and controls (p>0.05). The highly increased positive rates and scores of LMP7 of AMs were markedly associated with increased percentages of CD8+ T cells (%BAL total cells, r=0.43, p<0.05), decreased percentages of macrophages (r=–0.50, p<0.05) and worse pulmonary function indexes (p<0.05) in these granulomatous patients. The positive rates and scores of LMP2 expressed in AMs were not significantly different between patients with HP, sarcoidosis, and controls (all p>0.05). The positive rates and scores of LMP7 in AMs correlated with the values of LMP2 (p<0.01) in granulomatous patients.

Conclusion: The expression of immunoproteasomal LMP7, but not LMP2, was amplified in HP compared with sarcoidosis and controls, which suggests that LMP7 may be associated in the pathogenesis of HP.