ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Role of leukotriene A4 hydrolase aminopeptidase in the pathogenesis of emphysema.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Genome-Wide Association Analysis of Single-Breath DlAmerican journal of respiratory cell and molecular biology · 2019Trial
- Human genetic associations of the airway microbiome in chronic obstructive pulmonary disease.Respiratory research · 2024Article
- Review
- Serum Proteomic Profiling in Patients with Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2023Article
- Leukotriene A4 Hydrolase and Hepatocyte Growth Factor Are Risk Factors of Sudden Cardiac Death Due to First-Ever Myocardial Infarction.International journal of molecular sciences · 2022Article
- Substrate-dependent modulation of the leukotriene AScientific reports · 2022Article
- Proline-Glycine-Proline Peptides Are Critical in the Development of Smoke-induced Emphysema.American journal of respiratory cell and molecular biology · 2019Article
- Mesenchymal Stem Cell-Derived Extracellular Vesicles Decrease Lung Injury in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- The multifaceted roles of the matrikine Pro-Gly-Pro in pulmonary health and disease.European respiratory review : an official journal of the European Respiratory Society · 2018Review
- Article
- Analysis of the Effect of Intestinal Ischemia and Reperfusion on the Rat Neutrophils Proteome.Frontiers in molecular biosciences · 2018Article
- The arachidonic acid metabolism protein-protein interaction network and its expression pattern in esophageal diseases.American journal of translational research · 2018Article
- Feasibility and physiological relevance of designing highly potent aminopeptidase-sparing leukotriene A4 hydrolase inhibitors.Scientific reports · 2017Article
- The development of novel LTAScientific reports · 2017Article
- Inflammation-Generated Extracellular Matrix Fragments Drive Lung Metastasis.Cancer growth and metastasis · 2017Article
- Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.Endocrine-related cancer · 2016Article
- Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection.Nature communications · 2015Article
- Leukotriene A4 hydrolase: the Janus enzyme shows its ugly side in smokers.American journal of respiratory and critical care medicine · 2014Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The leukotriene A4 hydrolase (LTA4H) is a bifunctional enzyme with epoxy hydrolase and aminopeptidase activities. We hypothesize that the LTA4H aminopeptidase activity alleviates neutrophilic inflammation, which contributes to cigarette smoke (CS)-induced emphysema by clearing proline-glycine-proline (PGP), a triamino acid chemokine known to induce chemotaxis of neutrophils. To investigate the biological contributions made by the LTA4H aminopeptidase activity in CS-induced emphysema, we exposed wild-type mice to CS over 5 mo while treating them with a vehicle or a pharmaceutical agent (4MDM) that selectively augments the LTA4H aminopeptidase without affecting the bioproduction of leukotriene B4. Emphysematous phenotypes were assessed by premortem lung physiology with a small animal ventilator and by postmortem histologic morphometry. CS exposure acidified the airspaces and induced localization of the LTA4H protein into the nuclei of the epithelial cells. This resulted in accumulation of PGP in the airspaces by suppressing the LTA4H aminopeptidase activity. When the LTA4H aminopeptidase activity was selectively augmented by 4MDM, the levels of PGP in the bronchoalveolar lavage fluid and infiltration of neutrophils into the lungs were significantly reduced without affecting the levels of leukotriene B4. This protected murine lungs from CS-induced emphysematous alveolar remodeling. In conclusion, CS exposure promotes the development of CS-induced emphysema by suppressing the enzymatic activities of the LTA4H aminopeptidase in lung tissues and accumulating PGP and neutrophils in the airspaces. However, restoring the leukotriene A4 aminopeptidase activity with a pharmaceutical agent protected murine lungs from developing CS-induced emphysema.
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Registered trials
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