ArticleAmerican journal of respiratory cell and molecular biology2015
A pneumocyte-macrophage paracrine lipid axis drives the lung toward fibrosis.
Article in American journal of respiratory cell and molecular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 161 citations in OpenAlex.
- Lipid Uptake by Alveolar Macrophages Drives Fibrotic Responses to Silica Dust.Scientific reports · 2019Trial
- Transcriptional factor KLF9 in pulmonary fibrosis: from molecular mechanisms to precision intervention-a narrative review.Journal of thoracic disease · 2026Review
- Circulating lipids, lipoproteins, and the risk of idiopathic pulmonary fibrosis: a cohort study and genetic analysis.Journal of lipid research · 2026Article
- Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Potential association of bronchoalveolar lavage lipid-laden macrophages with disease severity and corticosteroid response in interstitial lung disease: a pilot study.Journal of thoracic disease · 2026Article
- Altered cholesterol immunometabolism activates the macrophage NLRP3-inflammasome in lung fibrosis.American journal of respiratory cell and molecular biology · 2026Article
- The triple-hit hypothesis: exploring pulmonary e-cigarette, PMEuropean respiratory review : an official journal of the European Respiratory Society · 2026Review
- Lipid and Foam Cell Accumulation as Novel Pathological Features of Benign Prostatic Hyperplasia.The Prostate · 2026Article
- Review
- Lipid Metabolism and Obesity in Early Life: Drivers of Chronic Lung Disease From Development to Adulthood.Molecular nutrition & food research · 2026Review
- Tamoxifen promotes metastasis of breast cancer via reshaping lipid-driven fibrotic microenvironments in the lung.Neoplasia (New York, N.Y.) · 2026Article
- Chronic IL-21 exposure reshapes pulmonary environment, elevating risk of respiratory diseases.Cellular and molecular life sciences : CMLS · 2026Article
- Micro- and Nanoplastics and Pulmonary Health: The Current State of Research.Microplastics (Basel, Switzerland) · 2026Article
- Roles of the Altitude-Adapted Immune Microenvironment in Pulmonary Vascular Remodeling in High-Altitude Pulmonary Hypertension: A Review.Medical science monitor : international medical journal of experimental and clinical research · 2026Review
- Pulmonary toxicity of polymethyl methacrylate nanoplastics via intratracheal intubation in mice.Scientific reports · 2026Article
- The impact of macrophage metabolism on idiopathic pulmonary fibrosis development and treatment prospectives.Frontiers in immunology · 2026Review
- The interplay of ferroptosis and oxidative stress in pulmonary fibrosis: from mechanisms to treatment.Frontiers in cell and developmental biology · 2026Review
- The gene regulatory networks shaping macrophage plasticity and altered function in fibrosis.Frontiers in immunology · 2026Review
- Role of Glycerophospholipid Metabolism in Epilepsy.Current neuropharmacology · 2026Review
- Cholesterol-mediated inflammation activation in alveolar macrophages.BMC biology · 2025Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Lipid-laden macrophages, or "foam cells," are observed in the lungs of patients with fibrotic lung disease, but their contribution to disease pathogenesis remains unexplored. Here, we demonstrate that fibrosis induced by bleomycin, silica dust, or thoracic radiation promotes early and sustained accumulation of foam cells in the lung. In the bleomycin model, we show that foam cells arise from neighboring alveolar epithelial type II cells, which respond to injury by dumping lipids into the distal airspaces of the lungs. We demonstrate that oxidized phospholipids accumulate within alveolar macrophages (AMs) after bleomycin injury and that murine and human AMs treated with oxidized phosphatidylcholine (oxPc) become polarized along an M2 phenotype and display enhanced production of transforming growth factor-β1. The direct instillation of oxPc into the mouse lung induces foam cell formation and triggers a severe fibrotic reaction. Further, we show that reducing pulmonary lipid clearance by targeted deletion of the lipid efflux transporter ATP-binding cassette subfamily G member 1 increases foam cell formation and worsens lung fibrosis after bleomycin. Conversely, we found that treatment with granulocyte-macrophage colony-stimulating factor attenuates fibrotic responses, at least in part through its ability to decrease AM lipid accumulation. In summary, this work describes a novel mechanism leading to foam cell formation in the mouse lung and suggests that strategies aimed at blocking foam cell formation might be effective for treating fibrotic lung disorders.
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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.