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

ABSTRACT: 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

SUBMITTER: Genschmer KR 

PROVIDER: S-EPMC6368091 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature