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Kammerl, I.E. ; Dann, A. ; Mossina, A. ; Brech, D. ; Lukas, C. ; Vosyka, O. ; Nathan, P. ; Conlon, T.M. ; Wagner, D.E. ; Overkleeft, H.S.* ; Prasse, A.* ; Rosas, I.O.* ; Straub, T.* ; Krauss-Etschmann, S.* ; Königshoff, M. ; Preissler, G.* ; Winter, H.* ; Lindner, M.* ; Hatz, R.A.* ; Behr, J. ; Heinzelmann, K. ; Yildirim, A.Ö. ; Nößner, E. ; Eickelberg, O. ; Meiners, S.

Impairment of immunoproteasome function by cigarette smoke and in COPD.

Am. J. Respir. Crit. Care Med. 193, 1230-1241 (2016)
Publ. Version/Full Text Postprint DOI PMC
Open Access Green
RATIONALE: Chronic obstructive pulmonary disease patients and in particular smokers are more susceptible to respiratory infections contributing to acute exacerbations of disease. The immunoproteasome is a specialized type of proteasome destined to improve major histocompatibility complex (MHC) class I-mediated antigen presentation for the resolution of intracellular infections. OBJECTIVES: To characterize immunoproteasome function in COPD and its regulation by cigarette smoke. METHODS: Immunoproteasome expression and activity were determined in bronchoalveolar lavage (BAL) and lungs of human donors, COPD, and IPF patients, as well as in cigarette smoke-exposed mice. Smoke-mediated alteration of immunoproteasome activity and MHC I surface expression were analysed in human blood-derived macrophages. Immunoproteasome-specific MHC I antigen presentation was evaluated in spleen and lung immune cells that had been smoke-exposed in vitro or in vivo. MEASUREMENTS AND MAIN RESULTS: Immunoproteasome and MHC I mRNA expression was reduced in BAL cells of COPD patients and in isolated alveolar macrophages of COPD and IPF patients. Exposure of immune cells to cigarette smoke extract in vitro reduced immunoproteasome activity and impaired immunoproteasome-specific MHC I antigen presentation. In vivo, acute cigarette smoke exposure dynamically regulated immunoproteasome function and MHC I antigen presentation in mouse BAL cells. End-stage COPD lungs showed markedly impaired immunoproteasome activities. CONCLUSIONS: We here show for the first time that the activity of the immunoproteasome is impaired by cigarette smoke resulting in reduced MHC I antigen presentation. Regulation of immunoproteasome function by cigarette smoke may thus alter adaptive immune responses and add to prolonged infections and exacerbations in COPD and IPF.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mhc Class I Antigen Presentation ; Alveolar Macrophages ; Cigarette Smoke ; Immunoproteasome; Class-i; Macrophage Activation; Antigen Presentation; Acute Exacerbations; Induced Emphysema; T-lymphocytes; Alveolar; Mice; Proteasome; Inflammation
ISSN (print) / ISBN 1073-449X
e-ISSN 1535-4970
Journal American Journal of Respiratory and Critical Care Medicine
Quellenangaben Volume: 193, Issue: 11, Pages: 1230-1241 Article Number: , Supplement: ,
Publisher American Thoracic Society
Publishing Place New York
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
Institute of Virology (VIRO)