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Zöller, M. ; Mayr, C.H. ; Mastalerz, M. ; Dick, E. ; Chakraborty, A. ; Nakayma, M. ; Simon, L. ; Merl-Pham, J. ; Behr, J.* ; Hilgendorff, A. ; Schmid, O. ; Hauck, S.M. ; Schiller, H. ; Staab-Weijnitz, C.A.*

Transient and Persistent Airway Proteome Changes Induced by Cigarette Smoke.

Am. J. Respir. Crit. Care Med. 211, A6856 - A6856 (2025)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Rationale: The airway epithelium serves as the first protective barrier against cigarette smoke (CS), which is a major cause of chronic lung disease (CLD). While transient and persistent transcriptomic changes in the bronchial epithelium as a result of CS exposure have been described, proteomic studies are lacking in this context. Objective: To uncover CS-induced effects on the human airway proteome and identify the cellular source of transient and persistent changes. Methods: Label-free tandem mass spectrometry-based proteomics data of bronchoalveolar lavage fluid (BALF) from a CLD patient cohort mainly composed of interstitial lung disease (ILD) patients (n=124; 16 idiopathic pulmonary fibrosis (IPF), 79 non-IPF ILD, 29 non-ILD1) was analyzed in respect of patients' smoking history (ex-, active- and never-smokers). Results were compared to the proteome of chronically CS-exposed primary human bronchial epithelial cells (phBECs) relative to unexposed controls. Cellular sources of persistent protein changes were explored using immunofluorescent stainings of human lung tissue and whole lung single cell RNA-Seq analysis. Results: Smoking was associated with transient (up in active but lost in ex-smokers) and persistent (up in active and sustained in ex-smokers) protein changes in the BALF samples. We observed an overlap between CS-induced protein changes in phBECs and transient changes in BALF. Proteins associated with the persistent response primarily localized to macrophages as well as to basal and ciliated cells, but not to secretory cells, in the bronchial epithelium. Conclusion: CS triggers both transient and persistent protein changes in BALF of CLD patients. While the transient expression changes likely originate from the bronchial epithelium, persistent changes stem from both bronchial epithelial cells and macrophages. The results warrant further investigation into the relevance of these changes for onset and progression of CS-associated CLD. 1Mayr CH, et al. Integrative analysis of cell state changes in lung fibrosis with peripheral protein biomarkers. EMBO Mol Med 13: e12871, 2021.
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Publication type Article: Journal article
Document type Meeting abstract
Corresponding Author
Keywords Proteome ; Transient (computer Programming)
ISSN (print) / ISBN 1073-449X
e-ISSN 1535-4970
Journal American Journal of Respiratory and Critical Care Medicine
Quellenangaben Volume: 211, Issue: Abstracts, Pages: A6856 - A6856 Article Number: , Supplement: ,
Publisher American Thoracic Society
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Lung Health and Immunity (LHI)
Research Unit Precision Regenerative Medicine (PRM)
Institute of Computational Biology (ICB)
CF Metabolomics & Proteomics (CF-MPC)