Impairment of Immunoproteasome Function by Cigarette Smoke and in Chronic Obstructive Pulmonary Disease

Patients with chronic obstructive pulmonary disease (COPD) 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) clas...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2016-06, Vol.193 (11), p.1230-1241
Main Authors: Kammerl, Ilona E, Dann, Angela, Mossina, Alessandra, Brech, Dorothee, Lukas, Christina, Vosyka, Oliver, Nathan, Petra, Conlon, Thomas M, Wagner, Darcy E, Overkleeft, Hermen S, Prasse, Antje, Rosas, Ivan O, Straub, Tobias, Krauss-Etschmann, Susanne, Königshoff, Melanie, Preissler, Gerhard, Winter, Hauke, Lindner, Michael, Hatz, Rudolf, Behr, Jürgen, Heinzelmann, Katharina, Yildirim, Ali Ö, Noessner, Elfriede, Eickelberg, Oliver, Meiners, Silke
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Animals
Disease Models, Animal
Female
Humans
Immunoproteins - physiology
Male
Mice
Mice, Inbred C57BL
Middle Aged
Nicotiana
Pulmonary Disease, Chronic Obstructive - physiopathology
Smoke - adverse effects
Smoking - physiopathology
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Summary:Patients with chronic obstructive pulmonary disease (COPD) 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. To characterize immunoproteasome function in COPD and its regulation by cigarette smoke. Immunoproteasome expression and activity were determined in bronchoalveolar lavage (BAL) and lungs of human donors and patients with COPD or idiopathic pulmonary fibrosis (IPF), as well as in cigarette smoke-exposed mice. Smoke-mediated alterations of immunoproteasome activity and MHC I surface expression were analyzed 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. Immunoproteasome and MHC I mRNA expression was reduced in BAL cells of patients with COPD and in isolated alveolar macrophages of patients with COPD or IPF. 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. We here show 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.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.201506-1122oc