The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung
Open accessAbstract
Summary: Here we describe a novel pathogenic entity, the activated neutrophil (PMN)-derived exosome. These CD63+/CD66b+ nanovesicles acquire surface-bound neutrophil elastase (NE) during PMN degranulation, NE being oriented in a configuration resistant to αl-antitrypsin (α1AT). These exosomes bind and degrade extracellular matrix (ECM) via the integrin Mac-1 and NE respectively, causing the hallmarks of chronic obstructive pulmonary disease (COPD). Due to both ECM targeting and alAT resistance, exosomal NE is far more potent than free NE. Importantly, such PMN-derived exosomes exist in clinical specimens from subjects with COPD but not healthy controls, and are capable of transferring a COPD-like phenotype from humans to mice in an NE-driven manner. Similar findings were observed for another neutrophil-driven disease of ECM remodeling (bronchopulmonary dysplasia, BPD). These findings reveal an unappreciated role for exosomes in the pathogenesis of disorders of ECM homeostasis such as COPD and BPD, providing a critical mechanism for proteolytic damage.
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Metadata
- Authors
- Genschmer, K. R., Russell, D. W., Lal, C., Szul, T., Bratcher, P. E., Noerager, B. D., Abdul Roda, M., Xu, X., Rezonzew, G., Viera, L., Dobosh, B. S., Margaroli, C., Abdalla, T. H., King, R. W., McNicholas, C. M., Wells, J. M., Dransfield, M. T., Tirouvanziam, R., Gaggar, A., & Blalock, J. E.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 176
- Issue
- 1-2
- Pages
- 113-126.e15
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2909520779
- Cited by
- 445
- References
- 52
- FWCI
- 16.61
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Genschmer, K. R., Russell, D. W., Lal, C., Szul, T., Bratcher, P. E., Noerager, B. D., Abdul Roda, M., Xu, X., Rezonzew, G., Viera, L., Dobosh, B. S., Margaroli, C., Abdalla, T. H., King, R. W., McNicholas, C. M., Wells, J. M., Dransfield, M. T., Tirouvanziam, R., Gaggar, A., & Blalock, J. E. (2019). Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung. Cell. https://doi.org/10.1016/j.cell.2018.12.002
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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