ArticleThe Journal of clinical investigation2003
Endothelium-derived Toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 172 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
172 citing papers in PubMed, 406 citations in OpenAlex.
- In vivo Cytokine Adsorption Reveals Distinct Neutrophil Mobilization Pathways during Experimental Human Endotoxemia.Journal of innate immunity · 2026Trial
- A developmentally informed narrative review of Toll-like receptors in adult and pediatric acute respiratory distress syndrome.Annals of translational medicine · 2026Review
- Condensation of cGAS induced by TyrScience signaling · 2026Article
- A modified hot phenol-based protocol for high-purity Escherichia coli lipopolysaccharide extraction: Biochemical validation, stem cell cytotoxicity, and dose dependent multi-organ inflammation in a rat model.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- Therapeutic targeting of endothelial calcium signaling accelerates the resolution of lung injury.Signal transduction and targeted therapy · 2025Article
- Advanced Nanoparticle Therapeutics for Targeting Neutrophils in Inflammatory Diseases.Advanced healthcare materials · 2025Review
- Neutrophils in Tissue Injury and Repair: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- Review
- Gut-lung immunometabolic crosstalk in sepsis: from microbiota to respiratory failure.Frontiers in medicine · 2025Review
- Acupuncture at Zusanli (ST36) for the benefits of sepsis-laboratory evidence for "preventive treatment of disease" and "holistic concept" in the protective effects of acupuncture: a literature review of rodent studies.Frontiers in neurology · 2025Review
- Exposure to bacterial PAMPs before RSV infection exacerbates innate inflammation and disease via IL-1α and TNF-α.Mucosal immunology · 2024Article
- Made to order: emergency myelopoiesis and demand-adapted innate immune cell production.Nature reviews. Immunology · 2024Review
- IL-22 Binding Protein Controls IL-22-Driven Bleomycin-Induced Lung Injury.The American journal of pathology · 2024Article
- Article
- Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response?Frontiers in immunology · 2024Review
- Bacteria-derived extracellular vesicles: endogenous roles, therapeutic potentials and their biomimetics for the treatment and prevention of sepsis.Frontiers in immunology · 2024Review
- Pyroptosis-induced inflammation and tissue damage.Seminars in immunology · 2023Review
- Single-cell epitope-transcriptomics reveal lung stromal and immune cell response kinetics to nanoparticle-delivered RIG-I and TLR4 agonists.Biomaterials · 2023Article
- Neutrophilia in severe asthma is reduced in Ormdl3 overexpressing mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- When the allergy alarm bells toll: The role of Toll-like receptors in allergic diseases and treatment.Frontiers in molecular biosciences · 2023Review
112 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The rapid and selective accumulation of neutrophils into the lungs is thought to underlie the pulmonary failure that leads to sepsis-related death. In this study we investigated whether neutrophil TLR4 is important in LPS-induced pulmonary neutrophil recruitment by creating chimeric mice (transferring bone marrow between TLR4(+/+) and TLR4(-/-) mice). In TLR4(+/+) mice receiving TLR4(-/-) bone marrow, 6 weeks after transplant TLR4 was absent in all circulating leukocytes as well as in resident macrophages (these mice were termed LeukocyteTLR4(-/-)), and these cells were completely nonresponsive to LPS. In TLR4(-/-) mice receiving TLR4(+/+) bone marrow, endothelial cells but not leukocytes were deficient in TLR4 (EndotheliumTLR4(-/-)). Surprisingly, systemic LPS (0.5 mg/kg) induced a dramatic increase in neutrophil sequestration into the lungs of LeukocyteTLR4(-/-) mice over the first 4 hours. Concomitantly, numbers of circulating leukocytes decreased by 90%. By contrast, EndotheliumTLR4(-/-) mice showed very little increase in neutrophil sequestration in the lungs, suggesting that endothelium rather than leukocyte TLR4 was important. Intravital microscopy of peripheral microcirculation in the cremaster muscle revealed about 30-fold more leukocyte-endothelial cell interactions in LPS-treated EndotheliumTLR4(-/-) mice than in LPS-treated LeukocyteTLR4(-/-) mice. This is consistent with less sequestration of leukocytes into the lungs of EndotheliumTLR4(-/-) mice. In conclusion, our data challenge the view that LPS directly activates neutrophils to trap in lungs and suggest a far more important role than previously appreciated for the endothelial cells.
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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.