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Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung.
Genschmer, Kristopher R; Russell, Derek W; Lal, Charitharth; Szul, Tomasz; Bratcher, Preston E; Noerager, Brett D; Abdul Roda, Mojtaba; Xu, Xin; Rezonzew, Gabriel; Viera, Liliana; Dobosh, Brian S; Margaroli, Camilla; Abdalla, Tarek H; King, Robert W; McNicholas, Carmel M; Wells, J Michael; Dransfield, Mark T; Tirouvanziam, Rabindra; Gaggar, Amit; Blalock, J Edwin.
Afiliación
  • Genschmer KR; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at
  • Russell DW; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at
  • Lal C; Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Translational Research in Disordered and Normal Development Program, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at
  • Szul T; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Bratcher PE; Department of Pediatrics, National Jewish Medical Center, Denver, CO 80206, USA.
  • Noerager BD; University of Montevallo, Montevallo, AL 35115, USA.
  • Abdul Roda M; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • Xu X; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Gregory Fleming James Cystic Fibrosis Research Ce
  • Rezonzew G; Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Translational Research in Disordered and Normal Development Program, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at
  • Viera L; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at
  • Dobosh BS; Department of Pediatrics, Center of CF and Airways Disease Research, and Program in Immunology and Molecular Pathogenesis, Emory University, Atlanta, GA, USA.
  • Margaroli C; Department of Pediatrics, Center of CF and Airways Disease Research, and Program in Immunology and Molecular Pathogenesis, Emory University, Atlanta, GA, USA.
  • Abdalla TH; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • King RW; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • McNicholas CM; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, The University of Alabama at Birmingham, Birmingh
  • Wells JM; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at
  • Dransfield MT; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, The University
  • Tirouvanziam R; Department of Pediatrics, Center of CF and Airways Disease Research, and Program in Immunology and Molecular Pathogenesis, Emory University, Atlanta, GA, USA.
  • Gaggar A; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at
  • Blalock JE; Department of Medicine, Division of Pulmonary, Allergy, and Critical Care, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Lung Health Center, The University of Alabama at Birmingham, Birmingham, AL 35294, USA; Program in Protease and Matrix Biology, The University of Alabama at
Cell ; 176(1-2): 113-126.e15, 2019 01 10.
Article en En | MEDLINE | ID: mdl-30633902
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 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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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Exosomas / Neutrófilos Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Año: 2019 Tipo del documento: Article
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Exosomas / Neutrófilos Límite: Animals / Female / Humans / Male Idioma: En Revista: Cell Año: 2019 Tipo del documento: Article