Matches in SemOpenAlex for { <https://semopenalex.org/work/W4240467856> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W4240467856 abstract "Abstract BackgroundAlpha-1 antitrypsin (AAT) is a major serine protease inhibitor. AAT deficiency (AATD) is a genetic disorder characterized by early-onset severe emphysema. In well-selected AATD patients, therapy with plasma-derived AAT (pAAT), “augmentation therapy”, provides modest clinical improvement but is perceived as cumbersome with weekly intravenous infusions. Using mouse models of emphysema, we compared the effects of a recombinant AAT-IgG1 Fc-fusion protein (AAT-Fc), which is expected to have a longer half-life following infusion, to those of pAAT. MethodsIn an elastase model of emphysema, mice received a single intratracheal instillation of porcine pancreatic elastase (PPE) or human leucocyte elastase (hLE). AAT-Fc, pAAT, or vehicle was administered intraperitoneally 1 day prior to or 3 weeks following elastase instillation. Lung function and histology assessments were performed at 7 and 32 days after elastase instillation. In a cigarette smoke (CS) model of emphysema, mice were exposed to CS daily, 5 days a week, for 6 months and AAT-Fc, pAAT, or vehicle were administered every 10 days during the last 3 months of CS exposure. Assessments were performed 3 days after the last CS exposure. Immune responses to lung elastin peptide (EP) and the effects of AAT-Fc or pAAT treatment on dendritic cell (DC) function were determined ex vivo . ResultsBoth elastase instillation and CS exposure triggered emphysema-like alveolar enlargement, increased lung compliance, and increased markers of inflammation compared to controls. Administration of AAT-Fc either prior to or following elastase instillation or during CS exposure provided greater protection than pAAT against alveolar enlargement, lung dysfunction, and airway inflammation. When challenged ex vivo with EP, spleen mononuclear cells from elastase-exposed mice exhibited dose-dependent production of IFNg and IL-17, suggesting immune reactivity. In co-culture experiments with splenic CD4 + T cells isolated from elastase-exposed mice, AAT-Fc treatment prior to EP-priming of bone marrow-derived dendritic cells inhibited the production of IFNg and IL-17. ConclusionsCompared to pAAT, AAT-Fc more effectively prevented or attenuated elastase- and CS-induced models of emphysema. These effects were associated with immunomodulatory effects on DC activity. AAT-Fc may provide a therapeutic option to individuals with AATD- and CS-induced emphysema." @default.
- W4240467856 created "2022-05-12" @default.
- W4240467856 creator A5023960478 @default.
- W4240467856 creator A5026411789 @default.
- W4240467856 creator A5038067008 @default.
- W4240467856 creator A5038777816 @default.
- W4240467856 creator A5087965827 @default.
- W4240467856 date "2021-02-09" @default.
- W4240467856 modified "2023-09-29" @default.
- W4240467856 title "Therapeutic Benefits of Recombinant Alpha1-Antitrypsin IgG1 Fc-Fusion Protein in Experimental Emphysema" @default.
- W4240467856 doi "https://doi.org/10.21203/rs.3.rs-180870/v1" @default.
- W4240467856 hasPublicationYear "2021" @default.
- W4240467856 type Work @default.
- W4240467856 citedByCount "0" @default.
- W4240467856 crossrefType "posted-content" @default.
- W4240467856 hasAuthorship W4240467856A5023960478 @default.
- W4240467856 hasAuthorship W4240467856A5026411789 @default.
- W4240467856 hasAuthorship W4240467856A5038067008 @default.
- W4240467856 hasAuthorship W4240467856A5038777816 @default.
- W4240467856 hasAuthorship W4240467856A5087965827 @default.
- W4240467856 hasConcept C126322002 @default.
- W4240467856 hasConcept C142724271 @default.
- W4240467856 hasConcept C150903083 @default.
- W4240467856 hasConcept C181199279 @default.
- W4240467856 hasConcept C185592680 @default.
- W4240467856 hasConcept C203014093 @default.
- W4240467856 hasConcept C207001950 @default.
- W4240467856 hasConcept C26291073 @default.
- W4240467856 hasConcept C2776317360 @default.
- W4240467856 hasConcept C2776326425 @default.
- W4240467856 hasConcept C2776914184 @default.
- W4240467856 hasConcept C2777714996 @default.
- W4240467856 hasConcept C2779869378 @default.
- W4240467856 hasConcept C2781044401 @default.
- W4240467856 hasConcept C55493867 @default.
- W4240467856 hasConcept C71924100 @default.
- W4240467856 hasConcept C86803240 @default.
- W4240467856 hasConceptScore W4240467856C126322002 @default.
- W4240467856 hasConceptScore W4240467856C142724271 @default.
- W4240467856 hasConceptScore W4240467856C150903083 @default.
- W4240467856 hasConceptScore W4240467856C181199279 @default.
- W4240467856 hasConceptScore W4240467856C185592680 @default.
- W4240467856 hasConceptScore W4240467856C203014093 @default.
- W4240467856 hasConceptScore W4240467856C207001950 @default.
- W4240467856 hasConceptScore W4240467856C26291073 @default.
- W4240467856 hasConceptScore W4240467856C2776317360 @default.
- W4240467856 hasConceptScore W4240467856C2776326425 @default.
- W4240467856 hasConceptScore W4240467856C2776914184 @default.
- W4240467856 hasConceptScore W4240467856C2777714996 @default.
- W4240467856 hasConceptScore W4240467856C2779869378 @default.
- W4240467856 hasConceptScore W4240467856C2781044401 @default.
- W4240467856 hasConceptScore W4240467856C55493867 @default.
- W4240467856 hasConceptScore W4240467856C71924100 @default.
- W4240467856 hasConceptScore W4240467856C86803240 @default.
- W4240467856 hasLocation W42404678561 @default.
- W4240467856 hasOpenAccess W4240467856 @default.
- W4240467856 hasPrimaryLocation W42404678561 @default.
- W4240467856 hasRelatedWork W13175860 @default.
- W4240467856 hasRelatedWork W1330323 @default.
- W4240467856 hasRelatedWork W1402687 @default.
- W4240467856 hasRelatedWork W17106945 @default.
- W4240467856 hasRelatedWork W19634680 @default.
- W4240467856 hasRelatedWork W2856950 @default.
- W4240467856 hasRelatedWork W371148 @default.
- W4240467856 hasRelatedWork W4913624 @default.
- W4240467856 hasRelatedWork W5219062 @default.
- W4240467856 hasRelatedWork W7888183 @default.
- W4240467856 isParatext "false" @default.
- W4240467856 isRetracted "false" @default.
- W4240467856 workType "article" @default.