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Cited by 489

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

A Novel C5a Receptor-Tissue Factor Cross-Talk in Neutrophils Links Innate Immunity to Coagulation Pathways

Ritis, Konstantinos, Doumas, Michael, Mastellos, Dimitrios, Micheli, Anastasia, Giaglis, Stavros, Magotti, Paola, Rafail, Stavros, Kartalis, Georgios, Sideras, Paschalis, Lambris, John D·2006·The Journal of Immunology

Abstract

Neutrophils and complement are key sentinels of innate immunity and mediators of acute inflammation. Recent studies have suggested that inflammatory processes modulate thrombogenic pathways. To date, the potential cross-talk between innate immunity and thrombosis and the precise molecular pathway by which complement and neutrophils trigger the coagulation process have remained elusive. In this study, we demonstrate that antiphospholipid Ab-induced complement activation and downstream signaling via C5a receptors in neutrophils leads to the induction of tissue factor (TF), a key initiating component of the blood coagulation cascade. TF expression by neutrophils was associated with an enhanced procoagulant activity, as verified by a modified prothrombin time assay inhibited by anti-TF mAb. Inhibition studies using the complement inhibitor compstatin revealed that complement activation is triggered by antiphospholipid syndrome (APS) IgG and leads to the induction of a TF-dependent coagulant activity. Blockade studies using a selective C5a receptor antagonist and stimulation of neutrophils with recombinant human C5a demonstrated that C5a, and its receptor C5aR, mediate the expression of TF in neutrophils and thereby significantly enhance the procoagulant activity of neutrophils exposed to APS serum. These results identify a novel cross-talk between the complement and coagulation cascades that can potentially be exploited therapeutically in the treatment of APS and other complement-associated thrombotic diseases.

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Crossref · 10.4049/jimmunol.177.7.4794

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Metadata

Authors
Ritis, K., Doumas, M., Mastellos, D., Micheli, A., Giaglis, S., Magotti, P., Rafail, S., Kartalis, G., Sideras, P., & Lambris, J. D.
Venue
The Journal of Immunology
Published
2006-10-01
Volume
177
Issue
7
Pages
4794-4802
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1959181807
Cited by
489
References
46
FWCI
5.53
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: A Novel C5a Receptor-Tissue Factor Cross-Talk in Neutrophils Links Innate Immunity to Coagulation Pathways. https://app.cochat.ai/papers/10.4049/jimmunol.177.7.4794
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Ritis, K., Doumas, M., Mastellos, D., Micheli, A., Giaglis, S., Magotti, P., Rafail, S., Kartalis, G., Sideras, P., & Lambris, J. D. (2006). A Novel C5a Receptor-Tissue Factor Cross-Talk in Neutrophils Links Innate Immunity to Coagulation Pathways. The Journal of Immunology. https://doi.org/10.4049/jimmunol.177.7.4794

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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