Cited by 60Complement system in diseasesBiomarkers in Disease MechanismsCoagulation, Bradykinin, Polyphosphates, and Angioedema

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Heme Interacts with C1q and Inhibits the Classical Complement Pathway

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Roumenina, Lubka T., Radanova, Maria, Atanasov, Boris P., Popov, Krastio T., Kaveri, Srinivas V., Lacroix-Desmazes, Sébastien, Frémeaux-Bacchi, Véronique, Dimitrov, Jordan D.·2011·Journal of Biological Chemistry

Abstract

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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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)
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
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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CoChat. (2026). Citation check: Heme Interacts with C1q and Inhibits the Classical Complement Pathway. https://app.cochat.ai/papers/10.1074/jbc.m110.206136
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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