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Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung.

Cell (2019-01-12)
Kristopher R Genschmer, Derek W Russell, Charitharth Lal, Tomasz Szul, Preston E Bratcher, Brett D Noerager, Mojtaba Abdul Roda, Xin Xu, Gabriel Rezonzew, Liliana Viera, Brian S Dobosh, Camilla Margaroli, Tarek H Abdalla, Robert W King, Carmel M McNicholas, J Michael Wells, Mark T Dransfield, Rabindra Tirouvanziam, Amit Gaggar, J Edwin Blalock

Here, we describe a novel pathogenic entity, the activated PMN (polymorphonuclear leukocyte, i.e., neutrophil)-derived exosome. These CD63+/CD66b+ nanovesicles acquire surface-bound neutrophil elastase (NE) during PMN degranulation, NE being oriented in a configuration resistant to α1-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 α1AT 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.

Product Number
Product Description

Anti-CEACAM8 antibody produced in rabbit, affinity isolated antibody
DL-Dithiothreitol, for molecular biology, ≥98% (HPLC), ≥99% (titration)
Amphotericin B solution, 250 μg/mL in deionized water, 0.1 μm filtered, BioReagent, suitable for cell culture
DL-Glyceraldehyde 3-phosphate solution, 45-55 mg/mL in H2O
Ceftazidime hydrate, ≥90.0%, contains ~10% sodium carbonate as stabilizer
N-Methoxysuccinyl-Ala-Ala-Pro-Val p-nitroanilide, elastase substrate
Penta-O-galloyl-β-D-glucose hydrate, ≥96% (HPLC)

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