ArticleThe American journal of pathology2012
Plasmodium falciparum histones induce endothelial proinflammatory response and barrier dysfunction.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
What it found
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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
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Meta-analysis of Plasmodium falciparummBio · 2019Pooled it
- ETS-guided iPSC-endothelial models recapitulate malaria pathogenesis.EMBO molecular medicine · 2026Article
- Mechanisms of parasite-mediated disruption of brain vessels.FEBS letters · 2026Review
- Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.Nature communications · 2025Article
- Disseminated intravascular coagulation.Journal of intensive care · 2025Review
- Natural hemozoin and β-hematin induce tissue damage and apoptosis in human placental explants.Toxicology reports · 2025Article
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- Ionotropic purinergic receptor 7 (P2X7) channel structure and pharmacology provides insight regarding non-nucleotide agonism.Channels (Austin, Tex.) · 2024Review
- The Impact of Extracellular Histones and Absence of Toll-like Receptors on Cardiac Functional and Electrical Disturbances in Mouse Hearts.International journal of molecular sciences · 2024Article
- Epigenetic regulation of innate immune dynamics during inflammation.Journal of leukocyte biology · 2024Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Probing cerebral malaria inflammation in 3D human brain microvessels.Cell reports · 2023Article
- Extracellular histones trigger oxidative stress-dependent induction of the NF-kB/CAM pathway via TLR4 in endothelial cells.Journal of physiology and biochemistry · 2023Article
- Elevated plasma interleukin-8 as a risk factor for mortality in children presenting with cerebral malaria.Infectious diseases of poverty · 2023Article
- Circulating Histones to Detect and Monitor the Progression of Cancer.International journal of molecular sciences · 2023Review
- Different PfEMP1-expressing Plasmodium falciparum variants induce divergent endothelial transcriptional responses during co-culture.PloS one · 2023Article
- Putative SET-domain methyltransferases inVirulence · 2022Article
- The IL-33/ST2 Pathway in Cerebral Malaria.International journal of molecular sciences · 2022Review
- Article
- Diverse Malaria Presentations across National Institutes of Health South Asia International Center for Excellence in Malaria Research Sites in India.The American journal of tropical medicine and hygiene · 2022Article
10 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
9 authors at 5 institutions in 3 countries.
Funding
Abstract
Plasmodium falciparum is a protozoan parasite of human erythrocytes that causes the most severe form of malaria. Severe P. falciparum infection is associated with endothelial activation and permeability, which are important determinants of the outcome of the infection. How endothelial cells become activated is not fully understood, particularly with regard to the effects of parasite subcomponents. We demonstrated that P. falciparum histones extracted from merozoites (HeH) directly stimulated the production of IL-8 and other inflammatory mediators by primary human dermal microvascular endothelial cells through a signaling pathway that involves Src family kinases and p38 MAPK. The stimulatory effect of HeH and recombinant P. falciparum H3 (PfH3) was abrogated by histone-specific antibodies. The release of nuclear contents on rupture of infected erythrocytes was captured by live cell imaging and confirmed by detecting nucleosomes in the supernatants of parasite cultures. HeH and recombinant parasite histones also induced endothelial permeability through a charge-dependent mechanism that resulted in disruption of junctional protein expression and cell death. Recombinant human activated protein C cleaved HeH and PfH3 and abrogated their proinflammatory effects. Circulating nucleosomes of both human and parasite origin were detected in the plasma of patients with falciparum malaria and correlated positively with disease severity. These results support a pathogenic role for both host- and pathogen-derived histones in P. falciparum-caused malaria.
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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.