ArticleJCI insight2021
Alpha-1 antitrypsin deficiency impairs lung antibacterial immunity in mice.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- AAT/SERPINA1 Pi*Z variant linked to gestational length and preterm birth prevention via AAT in mice.Nature communications · 2026Article
- Dysregulated Protease Homeostasis Defines Primary FSGS.Kidney360 · 2026Article
- Impact of chronic obstructive pulmonary disease on mortality in elderly patients with hip fracture: A retrospective cohort study.PloS one · 2026Article
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- Hepatic SerpinA1 improves energy and glucose metabolism through regulation of preadipocyte proliferation and UCP1 expression.Nature communications · 2024Article
- Analysis of alpha-1-antitrypsin (AAT)-regulated, glucocorticoid receptor-dependent genes in macrophages reveals a novel host defense function of AAT.Physiological reports · 2024Article
- S100A9 is indispensable for survival of pneumococcal pneumonia in mice.PLoS pathogens · 2023Article
- Alpha-1-antitrypsin antagonizes COVID-19: a review of the epidemiology, molecular mechanisms, and clinical evidence.Biochemical Society transactions · 2023Review
- Innate immune responses in pneumonia.Pneumonia (Nathan Qld.) · 2023Review
- Neutrophil extracellular traps have auto-catabolic activity and produce mononucleosome-associated circulating DNA.Genome medicine · 2022Article
- Loss ofInternational journal of molecular sciences · 2022Article
- Recent advancements in understanding the genetic involvement of alpha-1 antitrypsin deficiency associated lung disease: a look at future precision medicine approaches.Expert review of respiratory medicine · 2022Review
- The collectin SP-A and its trimeric recombinant fragment protect alveolar epithelial cells from the cytotoxic and proinflammatory effects of human cathelicidinFrontiers in immunology · 2022Article
- α1-Antitrypsin attenuates acute rejection of orthotopic murine lung allografts.Respiratory research · 2021Article
- Boosted Pro-Inflammatory Activity in Human PBMCs by Lipopolysaccharide and SARS-CoV-2 Spike Protein Is Regulated by α-1 Antitrypsin.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alpha-1 antitrypsin (AAT) is a major inhibitor of serine proteases in mammals. Therefore, its deficiency leads to protease-antiprotease imbalance and a risk for developing lung emphysema. Although therapy with human plasma-purified AAT attenuates AAT deficiency-related emphysema, its impact on lung antibacterial immunity is poorly defined. Here, we examined the effect of AAT therapy on lung protective immunity in AAT-deficient (KO) mice challenged with Streptococcus pneumoniae. AAT-KO mice were highly susceptible to S. pneumoniae, as determined by severe lobar pneumonia and early mortality. Mechanistically, we found that neutrophil-derived elastase (NE) degraded the opsonophagocytically important collectins, surfactant protein A (SP-A) and D (SP-D), which was accompanied by significantly impaired lung bacterial clearance in S. pneumoniae-infected AAT-KO mice. Treatment of S. pneumoniae-infected AAT-KO mice with human AAT protected SP-A and SP-D from NE-mediated degradation and corrected the pulmonary pathology observed in these mice. Likewise, treatment with Sivelestat, a specific inhibitor of NE, also protected collectins from degradation and significantly decreased bacterial loads in S. pneumoniae-infected AAT-KO mice. Our findings show that NE is responsible for the degradation of lung SP-A and SP-D in AAT-KO mice affecting lung protective immunity in AAT deficiency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.