ArticleProceedings of the National Academy of Sciences of the United States of America2014
Hemolysis-induced lethality involves inflammasome activation by heme.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 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
206 citing papers in PubMed, 1 synthesis or guideline pooled it, 332 citations in OpenAlex.
- Off-label use of canakinumab in pediatric rheumatology and rare diseases.Frontiers in medicine · 2022Pooled it
- Inhaled steroids associated with decreased macrophage markers in nonasthmatic individuals with sickle cell disease in a randomized trial.Annals of hematology · 2019Trial
- N-acetylcysteine plus deferoxamine for patients with prolonged hypotension does not decrease acute kidney injury incidence: a double blind, randomized, placebo-controlled trial.Critical care (London, England) · 2016Trial
- Iron, inflammation, and early death in adults with sickle cell disease.Circulation research · 2015Trial
- Vitamin D alleviates intracerebral hemorrhage symptoms by modulating pro-inflammatory/anti-inflammatory phenotypic transformation of microglia through P2X7R activation of NLRP3.IBRO neuroscience reports · 2026Article
- Isolating viable bacteria from positive blood cultures: impedance cytometry analysis.Biomedical microdevices · 2026Article
- Activation of Platelet Caspase-1 and P-Selectin Over-Expression in Sickle Cell Disease Patients: An Involvement of NLRP3 Inflammasome?Journal of cellular and molecular medicine · 2026Article
- Adaptive Immune Remodeling in Sickle Cell Disease: Linking Hemolysis-Driven Inflammation to Immune Dysfunction.Experimental hematology · 2026Review
- Identification of scavenger receptor BI as a scavenger of free heme that is essential for protection against hemolysis.Nature communications · 2026Article
- Immunomodulatory activity of Inula viscosa (L.) compounds identified via LC-ESI-MS and their COX-2-targeted anti-inflammatory potential: in vitro, in vivo and in silico analysis.Journal of computer-aided molecular design · 2026Article
- Article
- Cytochrome bBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Sex determines cardiac and renal Vulnerability to chronic hemoglobin toxicity.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Galectin-3 Mediates Heme-Induced Multi-Organ Dysfunction by Modulating the Splenic Immune Microenvironment.Diseases (Basel, Switzerland) · 2026Article
- ALDH1a3 Protects Against Iron Overload-Induced Oxidative Stress and Mitochondrial Impairment in Renal Tubular Epithelial Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- Phospholipase PLA2G5-triggered hemolysis emerges as a contributor to sepsis lethality.The Journal of clinical investigation · 2026Article
- Single-Cell Analysis of Preeclamptic Cord Blood Mononuclear Cells Revealed Activation of Heme-Associated Signalling Pathways.Journal of cellular and molecular medicine · 2026Article
- Article
- Ginsenoside Rg2 attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3-mediated pyroptosis.Journal of neuroinflammation · 2026Article
146 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
The increase of extracellular heme is a hallmark of hemolysis or extensive cell damage. Heme has prooxidant, cytotoxic, and inflammatory effects, playing a central role in the pathogenesis of malaria, sepsis, and sickle cell disease. However, the mechanisms by which heme is sensed by innate immune cells contributing to these diseases are not fully characterized. We found that heme, but not porphyrins without iron, activated LPS-primed macrophages promoting the processing of IL-1β dependent on nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3). The activation of NLRP3 by heme required spleen tyrosine kinase, NADPH oxidase-2, mitochondrial reactive oxygen species, and K(+) efflux, whereas it was independent of heme internalization, lysosomal damage, ATP release, the purinergic receptor P2X7, and cell death. Importantly, our results indicated the participation of macrophages, NLRP3 inflammasome components, and IL-1R in the lethality caused by sterile hemolysis. Thus, understanding the molecular pathways affected by heme in innate immune cells might prove useful to identify new therapeutic targets for diseases that have heme release.
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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.