ArticleFrontiers in public health2013
Alpha-1 antitrypsin reduces severity of pseudomonas pneumonia in mice and inhibits epithelial barrier disruption and pseudomonas invasion of respiratory epithelial cells.
Article in Frontiers in public health, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Transthyretin is a novel innate immune effector against Gram negative bacteria.PLoS pathogens · 2026Article
- Case Report:Frontiers in immunology · 2026Article
- Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.Physiological reports · 2024Article
- Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme.Frontiers in immunology · 2024Article
- Alpha-1 antitrypsin inhibits fractalkine-mediated monocyte-lung endothelial cell interactions.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence.Biochemical Society transactions · 2023Review
- Circulating oxidative stress and acute phase protein levels in horses infested with ticks.Experimental & applied acarology · 2023Article
- Synthetic neutrophil extracellular traps dissect bactericidal contribution of NETs under regulation of α-1-antitrypsin.Science advances · 2023Article
- Lung Inflammation in alpha-1-antitrypsin deficient individuals with normal lung function.Respiratory research · 2023Article
- Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution.Theranostics · 2023Article
- α1-Antitrypsin Binds to the Glucocorticoid Receptor with Anti-Inflammatory and Antimycobacterial Significance in Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection.The Journal of clinical investigation · 2022Article
- Enoxaparin augments alpha-1-antitrypsin inhibition of TMPRSS2, a promising drug combination against COVID-19.Scientific reports · 2022Article
- Ceruletide and Alpha-1 Antitrypsin as a Novel Combination Therapy for Ischemic Stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Article
- Correlation between α1-Antitrypsin Deficiency and SARS-CoV-2 Infection: Epidemiological Data and Pathogenetic Hypotheses.Journal of clinical medicine · 2021Review
- Treatment with a neutrophil elastase inhibitor and ofloxacin reduces P. aeruginosa burden in a mouse model of chronic suppurative otitis media.NPJ biofilms and microbiomes · 2021Article
- Human serum proteins bind to Sporothrix schenckii conidia with differential effects on phagocytosis.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2021Article
- Exacerbations of Lung Disease in Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2021Article
- Hypothesis: Alpha-1-antitrypsin is a promising treatment option for COVID-19.Medical hypotheses · 2021Review
- Granulocyte-targeted therapies for airway diseases.Pharmacological research · 2020Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nosocomial pneumonia (NP) is the third most common hospital-acquired infection and the leading cause of death due to hospital-acquired infection in the US. During pneumonia and non-pneumonia severe illness, respiratory tract secretions become enriched with the serine protease neutrophil elastase (NE). Several NE activities promote onset and severity of NP. NE in the airways causes proteolytic tissue damage, augments inflammation, may promote invasion of respiratory epithelium by bacteria, and disrupts respiratory epithelial barrier function. These NE activities culminate in enhanced bacterial replication, impaired gas exchange, fluid intrusion into the airways, and loss of bacterial containment that can result in bacteremia. Therefore, neutralizing NE activity may reduce the frequency and severity of NP. We evaluated human alpha-1 antitrypsin (AAT), the prototype endogenous NE inhibitor, as a suppressor of bacterial pneumonia and pneumonia-related pathogenesis. In AAT(+/+) transgenic mice that express human AAT in lungs, mortality due to Pseudomonas aeruginosa (P.aer) pneumonia was reduced 90% compared to non-transgenic control animals. Exogenous human AAT given to non-transgenic mice also significantly reduced P.aer pneumonia mortality. P.aer-infected AAT(+/+) mice demonstrated reduced lung tissue damage, decreased bacterial concentrations in lungs and blood, and diminished circulating cytokine concentrations compared to infected non-transgenic mice. In vitro, AAT suppressed P.aer internalization into respiratory epithelial cells and inhibited NE or P.aer-induced disruption of epithelial cell barrier function. The beneficial effects of human AAT in murine P.aer pneumonia raise the possibility of AAT use as a prophylactic treatment for NP in humans, and suggest a role for AAT as an innate immune mediator.
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