ArticlePloS one2012
Haemozoin induces early cytokine-mediated lysozyme release from human monocytes through p38 MAPK- and NF-kappaB-dependent mechanisms.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Malaria pigment hemozoin drives M1 pro-inflammatory macrophage polarization in vitro.Scientific reports · 2025Article
- Hemozoin induces malaria via activation of DNA damage, p38 MAPK and neurodegenerative pathways in a human iPSC-derived neuronal model of cerebral malaria.Scientific reports · 2024Article
- Circadian Control of the Response of Macrophages to Plasmodium Spp.-Infected Red Blood Cells.ImmunoHorizons · 2024Article
- Differential Effect of Extracellular Vesicles Derived fromInternational journal of molecular sciences · 2023Article
- Hemozoin-induced activation of human monocytes toward M2-like phenotype is partially reversed by antimalarial drugs-chloroquine and artemisinin.MicrobiologyOpen · 2019Article
- Reduced Hsp70 and Glutamine in Pediatric Severe Malaria Anemia: Role of Hemozoin in Suppressing Hsp70 and NF-κB activation.Molecular medicine (Cambridge, Mass.) · 2016Article
- Tumor necrosis factor reduces Plasmodium falciparum growth and activates calcium signaling in human malaria parasites.Biochimica et biophysica acta · 2016Article
- Cell-free hemoglobin: a novel mediator of acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Host-pathogen interactions in malaria: cross-kingdom signaling and mitochondrial regulation.Current opinion in immunology · 2015Review
- Involvement of Nod2 in the innate immune response elicited by malarial pigment hemozoin.Microbes and infection · 2015Article
- Oxygen-Loaded Nanodroplets Effectively Abrogate Hypoxia Dysregulating Effects on Secretion of MMP-9 and TIMP-1 by Human Monocytes.Mediators of inflammation · 2015Article
- Correlation of biomarkers for parasite burden and immune activation with acute kidney injury in severe falciparum malaria.Malaria journal · 2014Article
- Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood-brain barrier integrity?Fluids and barriers of the CNS · 2014Article
- Hemozoin induces hepatic inflammation in mice and is differentially associated with liver pathology depending on the Plasmodium strain.PloS one · 2014Article
- Effect of malaria components on blood mononuclear cells involved in immune response.Asian Pacific journal of tropical biomedicine · 2013Review
- Natural haemozoin induces expression and release of human monocyte tissue inhibitor of metalloproteinase-1.PloS one · 2013Article
- The apoptotic volume decrease is an upstream event of MAP kinase activation during Staurosporine-induced apoptosis in HeLa cells.International journal of molecular sciences · 2012Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malarial pigment (natural haemozoin, HZ) is a ferriprotoporphyrin IX crystal produced by Plasmodium parasites after haemoglobin catabolism. HZ-fed human monocytes are functionally compromised, releasing increased amounts of pro-inflammatory molecules, including cytokines, chemokines and cytokine-related proteolytic enzyme Matrix Metalloproteinase-9 (MMP-9), whose role in complicated malaria has been recently suggested. In a previous work HZ was shown to induce through TNFalpha production the release of monocytic lysozyme, an enzyme stored in gelatinase granules with MMP-9. Here, the underlying mechanisms were investigated. Results showed that HZ lipid moiety promoted early but not late lysozyme release. HZ-dependent lysozyme induction was abrogated by anti-TNFalpha/IL-1 beta/MIP-1 alpha blocking antibodies and mimicked by recombinant cytokines. Moreover, HZ early activated either p38 MAPK or NF-kappaB pathways by inducing: p38 MAPK phosphorylation; cytosolic I-kappaB alpha phosphorylation and degradation; NF-kappaB nuclear translocation and DNA-binding. Inhibition of both routes through selected molecules (SB203580, quercetin, artemisinin, parthenolide) prevented HZ-dependent lysozyme release. These data suggest that HZ-triggered overproduction of TNFalpha, IL-1 beta and MIP-1 alpha mediates induction of lysozyme release from human monocytes through activation of p38 MAPK and NF-kappaB pathways, providing new evidence on mechanisms underlying the HZ-enhanced monocyte degranulation in falciparum malaria and the potential role for lysozyme as a new affordable marker in severe malaria.
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