Impairment of Immunoproteasome Function by Cigarette Smoke and in Chronic Obstructive Pulmonary Disease
| Autor: | Susanne Krauss-Etschmann, Alessandra Mossina, Tobias Straub, Oliver Vosyka, Dorothee Brech, Petra Nathan, Darcy E. Wagner, Rudolf Hatz, Hermen S. Overkleeft, Ivan O. Rosas, Elfriede Noessner, Gerhard Preissler, Ali Önder Yildirim, Hauke Winter, Ilona Kammerl, Antje Prasse, Thomas M. Conlon, Oliver Eickelberg, Melanie Königshoff, Katharina Heinzelmann, Christina Lukas, Angela Dann, Silke Meiners, Michael Lindner, Jürgen Behr |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pulmonary and Respiratory Medicine Immunoproteins Antigen presentation Spleen Critical Care and Intensive Care Medicine Major histocompatibility complex Mice Pulmonary Disease Chronic Obstructive 03 medical and health sciences 0302 clinical medicine Immune system Smoke Tobacco MHC class I Animals Humans Medicine Aged Aged 80 and over COPD Lung medicine.diagnostic_test biology business.industry Smoking Middle Aged respiratory system medicine.disease respiratory tract diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology Bronchoalveolar lavage medicine.anatomical_structure Immunology biology.protein Female business 030215 immunology |
| Zdroj: | American journal of respiratory and critical care medicine American journal of respiratory and critical care medicine, 193(11), 1230-1241 |
| ISSN: | 1535-4970 1073-449X |
| Popis: | RATIONALE\nChronic 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.\nOBJECTIVES\nTo characterize immunoproteasome function in COPD and its regulation by cigarette smoke.\nMETHODS\nImmunoproteasome 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.\nMEASUREMENTS AND MAIN RESULTS\nImmunoproteasome 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.\nCONCLUSIONS\nWe 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|