ArticleAmerican journal of physiology. Lung cellular and molecular physiology2009
Oxidized {alpha}1-antitrypsin stimulates the release of monocyte chemotactic protein-1 from lung epithelial cells: potential role in emphysema.
Article in American journal of physiology. Lung cellular and molecular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- Human Neutrophil Elastase and the Protein-Storm Axis: Reversible Synthetic Inhibitors in Inflammatory Disease.Molecules (Basel, Switzerland) · 2026Review
- Alpha-1 antitrypsin-glucocorticoid receptor axis: a new pathway in immune modulation.Molecular medicine (Cambridge, Mass.) · 2026Article
- α‑1 Antitrypsin is a potential target of inflammation and immunomodulation (Review).Molecular medicine reports · 2025Review
- Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?International journal of molecular sciences · 2023Article
- Re-mining serum proteomics data reveals extensive post-translational modifications upon Zika and dengue infection.Molecular omics · 2023Article
- Article
- Pulmonary toxicity of actual alveolar deposition concentrations of ultrafine particulate matters in human normal bronchial epithelial cell.Environmental science and pollution research international · 2021Article
- Article
- Exacerbations of Lung Disease in Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2021Article
- The Beneficial Effects of Antioxidants in Health And Diseases.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Engineering the serpin αProtein science : a publication of the Protein Society · 2020Review
- S-Nitrosylation of α1-Antitrypsin Triggers Macrophages Toward Inflammatory Phenotype and Enhances Intra-Cellular Bacteria Elimination.Frontiers in immunology · 2019Article
- Update on αBreathe (Sheffield, England) · 2018Review
- The Multifaceted Effects of Alpha1-Antitrypsin on Neutrophil Functions.Frontiers in pharmacology · 2018Review
- Relationships between chronic obstructive pulmonary disease and lung cancer: biological insights.Journal of thoracic disease · 2016Review
- Redox Imbalance in Lung Cancer of Patients with Underlying Chronic Respiratory Conditions.Molecular medicine (Cambridge, Mass.) · 2016Article
- Understanding Lung Deposition of Alpha-1 Antitrypsin in Acute Experimental Mouse Lung Injury Model Using Fluorescence Microscopy.International journal of molecular imaging · 2016Article
- T Helper Subsets, Peripheral Plasticity, and the Acute Phase Protein, α1-Antitrypsin.BioMed research international · 2015Review
- Z α1-antitrypsin confers a proinflammatory phenotype that contributes to chronic obstructive pulmonary disease.American journal of respiratory and critical care medicine · 2014Article
- Effect of cigarette smoke exposure and structural modifications on the α-1 Antitrypsin interaction with caspases.Molecular medicine (Cambridge, Mass.) · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
alpha(1)-Antitrypsin (AT) is a major elastase inhibitor within the lung. Oxidation of critical methionine residues in AT generates oxidized AT (Ox-AT), which has a greatly diminished ability to inhibit neutrophil elastase. This process may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD) by creating a functional deficiency of AT permitting lung destruction. We show here that Ox-AT promotes release of human monocyte chemoattractant protein-1 (MCP-1) and IL-8 from human lung type epithelial cells (A549) and normal human bronchial epithelial (NHBE) cells. Native, cleaved, polymeric AT and secretory leukoproteinase inhibitor (SLPI) and oxidized conformations of cleaved, polymeric AT and SLPI did not have any significant effect on MCP-1 and IL-8 secretion. These findings were supported by the fact that instillation of Ox-AT into murine lungs resulted in an increase in JE (mouse MCP-1) and increased macrophage numbers in the bronchoalveolar lavage fluid. The effect of Ox-AT was dependent on NF-kappaB and activator protein-1 (AP-1)/JNK. These findings have important implications. They demonstrate that the oxidation of methionines in AT by oxidants released by cigarette smoke or inflammatory cells not only reduces the antielastase lung protection, but also converts AT into a proinflammatory stimulus. Ox-AT generated in the airway interacts directly with epithelial cells to release chemokines IL-8 and MCP-1, which in turn attracts macrophages and neutrophils into the airways. The release of oxidants by these inflammatory cells could oxidize AT, perpetuating the cycle and potentially contributing to the pathogenesis of COPD. Furthermore, these data demonstrate that molecules such as oxidants, antiproteinases, and chemokines, rather than act independently, are likely to interact to cause emphysema.
Indexed as
Identifiers
What OpenQuestion holds
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.