ArticleAmerican journal of respiratory and critical care medicine2009
15-epi-lipoxin A4 inhibits myeloperoxidase signaling and enhances resolution of acute lung injury.
Article in American journal of respiratory and critical care medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 4 of them syntheses that pooled it.
What it found
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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
124 citing papers in PubMed, 4 syntheses or guidelines pooled it, 202 citations in OpenAlex.
- Association Between Prior Aspirin Use and Acute Respiratory Distress Syndrome Incidence in At-Risk Patients: A Systematic Review and Meta-Analysis.Frontiers in pharmacology · 2020Pooled it
- Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching.Critical care medicine · 2017Pooled it
- Prevention or Treatment of Ards With Aspirin: A Review of Preclinical Models and Meta-Analysis of Clinical Studies.Shock (Augusta, Ga.) · 2017Pooled it
- Effect of Antiplatelet Therapy on Acute Respiratory Distress Syndrome and Mortality in Critically Ill Patients: A Meta-Analysis.PloS one · 2016Pooled it
- Effect of aspirin on deaths associated with sepsis in healthy older people (ANTISEPSIS): a randomised, double-blind, placebo-controlled primary prevention trial.The Lancet. Respiratory medicine · 2021Trial
- Trial
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- Flavones induce neutrophil apoptosis by down-regulation of Mcl-1 via a proteasomal-dependent pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013Trial
- Inhibition of DYRK1B BY C81 impedes inflammatory processes in leukocytes by reducing STAT3 activity.Cellular and molecular life sciences : CMLS · 2025Article
- Specialized pro-resolving mediators in neutrophil apoptosis regulation: unlocking novel therapeutic potential in kidney diseases.Frontiers in immunology · 2025Review
- The potential of exogenous specialized pro-resolving mediators in protecting against sepsis-associated lung injury: a review.Frontiers in pharmacology · 2025Review
- Local Drug Delivery Systems as Novel Approach for Controlling NETosis in Periodontitis.Pharmaceutics · 2024Review
- Beyond host defense and tissue injury: the emerging role of neutrophils in tissue repair.American journal of physiology. Cell physiology · 2024Review
- Effects of neutrophil fate on inflammation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Specialized Pro-Resolving Lipid Mediators: Endogenous Roles and Pharmacological Activities in Infections.Molecules (Basel, Switzerland) · 2023Review
- Immunomodulation of periodontitis with SPMs.Frontiers in oral health · 2023Review
- Potential role of lipoxin in the management of COVID-19: a narrative review.Inflammopharmacology · 2022Review
- Myeloperoxidase: Regulation of Neutrophil Function and Target for Therapy.Antioxidants (Basel, Switzerland) · 2022Review
- Lipoxin alleviates oxidative stress: a state-of-the-art review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Review
- Article
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleApoptosis is essential for removal of neutrophils from inflamed tissues and efficient resolution of inflammation. Myeloperoxidase (MPO), abundantly expressed in neutrophils, not only generates cytotoxic oxidants but also signals through the beta(2) integrin Mac-1 to rescue neutrophils from constitutive apoptosis, thereby prolonging inflammation.
objectivesBecause aspirin-triggered 15-epi-lipoxin A(4) (15-epi-LXA(4)) modulates Mac-1 expression, we investigated the impact of 15-epi-LXA(4) on MPO suppression of neutrophil apoptosis and MPO-mediated neutrophil-dependent acute lung injury.
methodsHuman neutrophils were cultured with MPO with or without 15-epi-LXA(4) to investigate development of apoptosis. Acute lung injury was produced by intratracheal injection of carrageenan plus MPO or intraperitoneal injection of live Escherichia coli in mice, and the animals were treated with 15-epi-LXA(4) at the peak of inflammation. MEASUREMENTS AND MAIN
results15-Epi-LXA(4) through down-regulation of Mac-1 expression promoted apoptosis of human neutrophils by attenuating MPO-induced activation of extracellular signal-regulated kinase and Akt-mediated phosphorylation of Bad and by reducing expression of the antiapoptotic protein Mcl-1, thereby aggravating mitochondrial dysfunction. The proapoptotic effect of 15-epi-LXA(4) was dominant over MPO-mediated effects even when it was added at 4 hours post MPO. In mice, treatment with 15-epi-LXA(4) accelerated the resolution of established carrageenan plus MPO-evoked as well as E. coli-induced neutrophil-dependent pulmonary inflammation through redirecting neutrophils to caspase-mediated cell death and facilitating their removal by macrophages.
conclusionsThese results demonstrate that aspirin-triggered 15-epi-LXA(4) enhances resolution of inflammation by overriding the powerful antiapoptosis signal from MPO, thereby demonstrating a hitherto unrecognized mechanism by which aspirin promotes resolution of inflammation.
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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.