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Heme Interacts with C1q and Inhibits the Classical Complement Pathway
Open accessAbstract
C1q is the recognition subunit of the first component of the classical complement pathway. It participates in clearance of immune complexes and apoptotic cells as well as in defense against pathogens. Inappropriate activation of the complement contributes to cellular and tissue damage in different pathologies, urging the need for the development of therapeutic agents that are able to inhibit the complement system. In this study, we report heme as an inhibitor of C1q. Exposure of C1q to heme significantly reduced the activation of the classical complement pathway, mediated by C-reactive protein (CRP) and IgG. Interaction analyses revealed that heme reduces the binding of C1q to CRP and IgG. Furthermore, we demonstrated that the inhibition of C1q interactions results from a direct binding of heme to C1q. Formation of complex of heme with C1q caused changes in the mechanism of recognition of IgG and CRP. Taken together, our data suggest that heme is a natural negative regulator of the classical complement pathway at the level of C1q. Heme may play a role at sites of excessive tissue damage and hemolysis where large amounts of free heme are released.
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Sorted by citations
Complement System Part I – Molecular Mechanisms of Activation and Regulation
Merle, N. S., Church, S. E., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00262 · Cited by 1,620
Self-citationGavriilaki, E., Anagnostopoulos, A., & Mastellos, D. C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00337 · Cited by 106
Metadata
- Authors
- Roumenina, L. T., Radanova, M., Atanasov, B. P., Popov, K. T., Kaveri, S. V., Lacroix-Desmazes, S., Frémeaux-Bacchi, V., & Dimitrov, J. D.
- Affiliations
- Inserm (FR)
- Medical University of Varna (BG)
- Bulgarian Academy of Sciences (BG)
- German Cancer Research Center (DE)
- Corresponding author
- Roumenina, Lubka T.
- Dimitrov, Jordan D.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 286
- Issue
- 18
- Pages
- 16459-16469
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3091251
- OpenAlex
- W2026891407
- Cited by
- 60
- References
- 3
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 8 · 2019: 10 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 5 · 2012: 1
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Health Sciences › Medicine › Hematology › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Keywords
- heme, C1q, classical complement pathway, complement inhibition, C-reactive protein, IgG, protein-protein interaction, complement activation, hemolysis, tissue damage
- MeSH terms
- C-Reactive Protein, Complement Pathway, Classical, Heme, Hemolysis, Humans, Immunoglobulin G, Protein Binding, Complement C1q
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- Roumenina, L. T., Radanova, M., Atanasov, B. P., Popov, K. T., Kaveri, S. V., Lacroix-Desmazes, S., Frémeaux-Bacchi, V., & Dimitrov, J. D. (2011). Heme Interacts with C1q and Inhibits the Classical Complement Pathway. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m110.206136