biostudies-literatureGenschmer KRBLRD VAUAB Center for Free Radical BiologyUAB O’Brien Acute Kidney Injury CenterUAB Lung Health CenterNancy Dunlap ChairNIDDK NIH HHSNHLBI NIH HHSThe Gregory Fleming James CF CenterVeteran’s AffairsNIHComprehensive Cancer Center Core113-126.e15https://www.ebi.ac.uk/biostudies/studies/S-EPMC6368091biostudies-literatureUnknown176(1-2)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-drivenCellActivated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung.PMC6368091P30 CA031148R01 HL102371I01BX001756R01 HL114439R01 HL110950R01 HL077783I01 BX001756R01HL126596T32HL105346-07T32 HL105346R35HL135710K08 HL123940K08 HL141652R01 HL126603AHA-17SDG32720009R01 HL126596P30 DK079337R01HL114439P30 DK072482R01HL077783R01HL110950T32 HL105346-05R01HL102371K08HL123940R01HL126603R35 HL135710McNicholas CMGaggar ASzul TViera LDobosh BSBratcher PEAbdalla THTirouvanziam RLal CRezonzew GRussell DWNoerager BDAbdul Roda MKing RWWells JMMargaroli CBlalock JEDransfield MTGenschmer KRXu XfalseActivated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung.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-driven2019-01-01T00:00:00Z2019 Jan2026-04-14T21:17:52.271Z2020-05-22T07:35:33ZS-EPMC63680913063390210.1016/j.cell.2018.12.002