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Impairment of immunoproteasome function by cigarette smoke and in chronic obstructive pulmonary disease

Kammerl, Ilona E.; Dann, Angela; Mossina, Alessandra; Brech, Dorothee; Lukas, Christina; Vosyka, Oliver; Nathan, Petra; Conlon, Thomas M; Wagner, Darcy E. LU and Overkleeft, Hermen S., et al. (2016) In American Journal of Respiratory and Critical Care Medicine 193(11). p.1230-1241
Abstract

Rationale: Patients with chronic obstructive pulmonary disease (COPD) and in particular smokers aremore 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 and patientswith COPD or idiopathic pulmonary fibrosis (IPF), as well as in cigarette smoke-exposedmice. Smoke-mediated... (More)

Rationale: Patients with chronic obstructive pulmonary disease (COPD) and in particular smokers aremore 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 and patientswith COPD or idiopathic pulmonary fibrosis (IPF), as well as in cigarette smoke-exposedmice. Smoke-mediated alterations of immunoproteasome activity and MHC I surface expression were analyzed in human blood-derived macrophages. Immunoproteasomespecific 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 ImRNA expression was reduced in BAL cells of patients with COPD and in isolated alveolarmacrophages 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. Conclusions: 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.

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publication status
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keywords
Alveolar macrophages, Cigarette Smoke, Immunoproteasome, MHC class I Antigen Presentation
in
American Journal of Respiratory and Critical Care Medicine
volume
193
issue
11
pages
1230 - 1241
publisher
Am Thoracic Soc
external identifiers
  • scopus:84988813585
ISSN
1073-449X
DOI
10.1164/rccm.201506-1122OC
language
English
LU publication?
no
id
15b1ce82-d47c-4365-be7e-b46acae110cf
date added to LUP
2017-08-15 14:35:31
date last changed
2017-11-14 09:56:29
@article{15b1ce82-d47c-4365-be7e-b46acae110cf,
  abstract     = {<p>Rationale: Patients with chronic obstructive pulmonary disease (COPD) and in particular smokers aremore 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 and patientswith COPD or idiopathic pulmonary fibrosis (IPF), as well as in cigarette smoke-exposedmice. Smoke-mediated alterations of immunoproteasome activity and MHC I surface expression were analyzed in human blood-derived macrophages. Immunoproteasomespecific 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 ImRNA expression was reduced in BAL cells of patients with COPD and in isolated alveolarmacrophages 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. Conclusions: 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.</p>},
  author       = {Kammerl, Ilona E. and Dann, Angela and Mossina, Alessandra and Brech, Dorothee and Lukas, Christina and Vosyka, Oliver and Nathan, Petra and Conlon, Thomas M and Wagner, Darcy E. and Overkleeft, Hermen S. and Prasse, Antje and Rosas, Ivan O. and Straub, Tobias and Krauss-Etschmann, Susanne and Konigshoff, Melanie and Preissler, Gerhard and Winter, Hauke and Lindner, Michael and Hatz, Rudolf and Behr, Jurgen and Heinzelmann, Katharina and Yildirim, Ali O and Noessner, Elfriede and Eickelberg, Oliver and Meiners, Silke},
  issn         = {1073-449X},
  keyword      = {Alveolar macrophages,Cigarette Smoke,Immunoproteasome,MHC class I Antigen Presentation},
  language     = {eng},
  month        = {06},
  number       = {11},
  pages        = {1230--1241},
  publisher    = {Am Thoracic Soc},
  series       = {American Journal of Respiratory and Critical Care Medicine},
  title        = {Impairment of immunoproteasome function by cigarette smoke and in chronic obstructive pulmonary disease},
  url          = {http://dx.doi.org/10.1164/rccm.201506-1122OC},
  volume       = {193},
  year         = {2016},
}