ArticleThe Journal of clinical investigation2013
Lipocalin 2 deactivates macrophages and worsens pneumococcal pneumonia outcomes.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
What it found
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Who cites it
92 citing papers in PubMed, 148 citations in OpenAlex.
- A neutrophil subset defined by intracellular olfactomedin 4 is associated with mortality in sepsis.American journal of physiology. Lung cellular and molecular physiology · 2021Trial
- Lipocalin (LCN) 2 Mediates Pro-Atherosclerotic Processes and Is Elevated in Patients with Coronary Artery Disease.PloS one · 2015Trial
- Trial
- Article
- IFNγ shapes macrophage inflammatory responses by STAT1 isoform-specific epigenetic and transcriptional mechanisms.BMC genomics · 2026Article
- Cardiac Macrophages Promote Polarization of Macrophages toward M2 Phenotype to Improve Myocardial Remodeling via NGAL after Myocardial Infarction.Cell biochemistry and biophysics · 2025Article
- Mosaic Loss of Y Chromosome Defines a Proximal Tubular Cell State Associated with Recovery from DGF and of Allograft Quality and Functional Reserve Post DCD Kidney Transplantation.Annals of surgery · 2025Article
- Prolonged skin allograft survival by rM180 amelogenin in a murine skin transplantation model.Frontiers in immunology · 2025Article
- Lipocalin-2 and intestinal diseases.World journal of gastroenterology · 2024Review
- Potential of using an engineered indole lactic acid producing Escherichia coli Nissle 1917 in a murine model of colitis.Scientific reports · 2024Article
- CXCR2 perturbation promotesJournal of medical microbiology · 2024Article
- A single-cell atlas of the peripheral immune response in patients with influenza A virus infection.iScience · 2023Article
- Circulating markers of neutrophil activation and lung injury in pediatric pneumonia in low-resource settings.Pathogens and global health · 2023Article
- Lipocalin-2: A Nurturer of Tumor Progression and a Novel Candidate for Targeted Cancer Therapy.Cancers · 2023Review
- Lipocalin family proteins and their diverse roles in cardiovascular disease.Pharmacology & therapeutics · 2023Review
- LCN2 secreted by tissue-infiltrating neutrophils induces the ferroptosis and wasting of adipose and muscle tissues in lung cancer cachexia.Journal of hematology & oncology · 2023Article
- Lipocalin-2 promotes acute lung inflammation and oxidative stress by enhancing macrophage iron accumulation.International journal of biological sciences · 2023Article
- Increased lipocalin-2 expression in pulmonary inflammation and fibrosis.Frontiers in medicine · 2023Article
- Understanding How Minerals Contribute to Optimal Immune Function.Journal of immunology research · 2023Review
- The von Hippel-Lindau Tumor Suppressor Gene Mutations Modulate Lipocalin-2 Expression in Ferroptotic-Inflammatory Pathways.Oxidative medicine and cellular longevity · 2023Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages play a key role in responding to pathogens and initiate an inflammatory response to combat microbe multiplication. Deactivation of macrophages facilitates resolution of the inflammatory response. Deactivated macrophages are characterized by an immunosuppressive phenotype, but the lack of unique markers that can reliably identify these cells explains the poorly defined biological role of this macrophage subset. We identified lipocalin 2 (LCN2) as both a marker of deactivated macrophages and a macrophage deactivator. We show that LCN2 attenuated the early inflammatory response and impaired bacterial clearance, leading to impaired survival of mice suffering from pneumococcal pneumonia. LCN2 induced IL-10 formation by macrophages, skewing macrophage polarization in a STAT3-dependent manner. Pulmonary LCN2 levels were tremendously elevated during bacterial pneumonia in humans, and high LCN2 levels were indicative of a detrimental outcome from pneumonia with Gram-positive bacteria. Our data emphasize the importance of macrophage deactivation for the outcome of pneumococcal infections and highlight the role of LCN2 and IL-10 as determinants of macrophage performance in the respiratory tract.
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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.