ArticleThe Journal of clinical investigation2013
Extracellular hemin crisis triggers acute chest syndrome in sickle mice.
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 176 papers, 1 of them a synthesis that pooled it.
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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
176 citing papers in PubMed, 1 synthesis or guideline pooled it, 262 citations in OpenAlex.
- Role of innate immunity-triggered pathways in the pathogenesis of Sickle Cell Disease: a meta-analysis of gene expression studies.Scientific reports · 2015Pooled it
- Iron, inflammation, and early death in adults with sickle cell disease.Circulation research · 2015Trial
- Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor.Blood · 2014Trial
- Haemolytic injury and cardiovascular disease.Nature reviews. Cardiology · 2026Review
- Acute therapy with hemopexin (CSL889) resolves LPS-induced lung vaso-occlusion in sickle mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Identification of scavenger receptor BI as a scavenger of free heme that is essential for protection against hemolysis.Nature communications · 2026Article
- Exercise in Sickle Cell Disease: The Impact on Pathophysiology and Clinical Symptoms.Children (Basel, Switzerland) · 2026Review
- Targeting PAR1 biased signaling with parmodulin reduces thromboinflammation and acute lung injury in sickle cell disease.Blood advances · 2026Article
- Article
- Proteomic Analysis of Golden Sputum Reveals Pulmonary Complement Activation During Acute Chest Syndrome in Children With Sickle Cell Disease.American journal of hematology · 2026Article
- Artificial Oxygen Carriers: Lessons From Hemoglobin-Based Oxygen Carrier Clinical Trials and Current Development Efforts.Shock (Augusta, Ga.) · 2026Review
- Sustained expression of hemopexin in an animal model of sickle cell anemia.Blood vessels, thrombosis & hemostasis · 2026Article
- Thrombomodulin protects against acute vascular and multiorgan injury in sickle cell disease.JCI insight · 2026Article
- CD39 polymorphism enables lung thrombosis in sickle cell disease.Nature communications · 2026Article
- Acute Incompatible Red Blood Cell Transfusion in Mice.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Analysis of Biotinylated Red Blood Cells Following Transfusion.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Examination of Antigen-Specific B Cell Responses to Red Blood Cell Transfusion.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Flow Cytometric Examination of Galectin Binding to Red Blood Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- IFN-I-Mediated Transcriptional Reprogramming Drives Myeloid-skewed Hematopoiesis in Sickle Cell Anemia.Research square · 2025Article
- Emerging pathways in thromboinflammation of sickle cell disease: novel findings in disease pathogenesis.Research and practice in thrombosis and haemostasis · 2025Review
116 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 1 country.
Funding
Abstract
The prevention and treatment of acute chest syndrome (ACS) is a major clinical concern in sickle cell disease (SCD). However, the mechanism underlying the pathogenesis of ACS remains elusive. We tested the hypothesis that the hemolysis byproduct hemin elicits events that induce ACS. Infusion of a low dose of hemin caused acute intravascular hemolysis and autoamplification of extracellular hemin in transgenic sickle mice, but not in sickle-trait littermates. The sickle mice developed multiple symptoms typical of ACS and succumbed rapidly. Pharmacologic inhibition of TLR4 and hemopexin replacement therapy prior to hemin infusion protected sickle mice from developing ACS. Replication of the ACS-like phenotype in nonsickle mice revealed that the mechanism of lung injury due to extracellular hemin is independent of SCD. Using genetic and bone marrow chimeric tools, we confirmed that TLR4 expressed in nonhematopoietic vascular tissues mediated this lethal type of acute lung injury. Respiratory failure was averted after the onset of ACS-like symptoms in sickle mice by treating them with recombinant hemopexin. Our results reveal a mechanism that helps to explain the pathogenesis of ACS, and we provide proof of principle for therapeutic strategies to prevent and treat this condition in mice.
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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.