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doi:10.22028/D291-36763
Titel: | Blockade of PD-1 decreases neutrophilic inflammation and lung damage in experimental COPD |
VerfasserIn: | Ritzmann, Felix Borchardt, Kai Vella, Giovanna Chitirala, Praneeth Angenendt, Adrian Herr, Christian Menger, Michael D. Hoth, Markus Lis, Annette Bohle, Rainer M. Bals, Robert Beisswenger, Christoph |
Sprache: | Englisch |
Titel: | American Journal of Physiology : Lung Cellular and Molecular Physiology |
Bandnummer: | 320 |
Heft: | 5 |
Seiten: | L958–L968 |
Verlag/Plattform: | American Physiological Society |
Erscheinungsjahr: | 2021 |
Freie Schlagwörter: | COPD inflammation lung damage macrophages PD-1 PD-L1 |
DDC-Sachgruppe: | 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Chronic obstructive lung disease (COPD) and lung cancer are both caused by smoking and often occur as comorbidity. The programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis is an important canonic immunoregulatory pathway, and antibodies that specifically block PD-1 or PD-L1 have demonstrated efficacy as therapeutic agents for non-small cell lung cancer. The role of the PD-1/PD-L1 axis in the pathogenesis of COPD is unknown. Here, we analyzed the function of the PD-1/PD-L1 axis in preclinical COPD models and evaluated the concentrations of PD-1 and PD-L1 in human serum and bronchoalveolar lavage (BAL) fluids as biomarkers for COPD. Anti-PD-1 treatment decreased lung damage and neutrophilic inflammation in mice chronically exposed to cigarette smoke (CS) or nontypeable Haemophilus influenzae (NTHi). Ex vivo stimulated macrophages obtained from anti-PD-1-treated mice released reduced amounts of inflammatory cytokines. PD-L1 concentrations correlated positively with PD-1 concentrations in human serum and BAL fluids. Lung sections obtained from patients with COPD stained positive for PD-L1. Our data indicate that the PD-1/PD-L1 axis is involved in developing inflammation and tissue destruction in COPD. Inflammation-induced activation of the PD-1 pathway may contribute to disease progression. |
DOI der Erstveröffentlichung: | 10.1152/ajplung.00121.2020 |
URL der Erstveröffentlichung: | https://journals.physiology.org/doi/full/10.1152/ajplung.00121.2020 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-367634 hdl:20.500.11880/33404 http://dx.doi.org/10.22028/D291-36763 |
ISSN: | 1522-1504 1040-0605 |
Datum des Eintrags: | 11-Jul-2022 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplemental material |
In Beziehung stehendes Objekt: | https://figshare.com/ndownloader/files/26617658 |
Fakultät: | M - Medizinische Fakultät |
Fachrichtung: | M - Biophysik M - Chirurgie M - Innere Medizin M - Pathologie |
Professur: | M - Prof. Dr. Robert Bals M - Prof. Dr. Rainer M. Bohle M - Prof. Dr. Markus Hoth M - Prof. Dr. Michael D. Menger |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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