Complement C3b contributes to-induced platelet aggregation in human whole blood

INTRODUCTION: Platelets have essential functions as first responders in the immune response to pathogens. Activation and aggregation of platelets in bacterial infections can lead to life-threatening conditions such as arterial thromboembolism or sepsis-associated coagulopathy. METHODS: In this study, we investigated the role of complement in Escherichia coli (E. coli)-induced platelet aggregation in human whole blood, using Multiplate® aggregometry, flow cytometry, and confocal microscopy. RESULTS AND DISCUSSION: We found that compstatin, which inhibits the cleavage of complement component C3 to its components C3a and C3b, reduced the E. coli-induced platelet aggregation by 42%-76% (p = 0.0417). This C3-dependent aggregation was not C3a-mediated as neither inhibition of C3a using a blocking antibody or a C3a receptor antagonist, nor the addition of purified C3a had any effects. In contrast, a C3b-blocking antibody significantly reduced the E. coli-induced platelet aggregation by 67% (p = 0.0133). We could not detect opsonized C3b on platelets, indicating that the effect of C3 was not dependent on C3b-fragment deposition on platelets. Indeed, inhibition of glycoprotein IIb/IIIa (GPIIb/IIIa) and complement receptor 1 (CR1) showed that these receptors were involved in platelet aggregation. Furthermore, aggregation was more pronounced in hirudin whole blood than in hirudin platelet-rich plasma, indicating that E. coli-induced platelet aggregation involved other blood cells. In conclusion, the E. coli-induced platelet aggregation in human whole blood is partly C3b-dependent, and GPIIb/IIIa and CR1 are also involved in this process.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Platelets have essential functions as first responders in the immune response to pathogens.

Leech-derived molecules this paper discusses, each with a full profile in the ASH compound registry:

Explore cómo esta investigación se conecta con la práctica clínica

More peer-reviewed studies in Resistencia antimicrobiana.

• Novel Leech Antimicrobial Peptides — Hirunipins — Kumar et al. (2025)
• Leech therapy (Hirudo medicinalis) attenuates testicular damages induced by testicular ischemia/reperfusion in an animal model — Davoodi F et al. (2021)
• AIF-1 and RNASET2 Play Complementary Roles in the Innate Immune Response of Medicinal Leech — Baranzini N et al. (2019)
• Medicinal leech antimicrobial peptides lacking toxicity represent a promising alternative strategy to combat antibiotic-resistant pathogens — Grafskaia E et al. (2019)
• Antimicrobial Role of RNASET2 Protein During Innate Immune Response in the Medicinal Leech — Baranzini N et al. (2020)
• Morganella Morganii Infection in Hirudo Medicinalis (Iran): A Case Report — Rahmati Holasoo H et al. (2022)
• Clinical efficacy of Jalaukawacharana (leech application) in Thrombosed piles — Bhagat P, Raut S, Lakhapati A (2012)
• Determination of disulfide linkages in antimicrobial peptides of the macin family by combination of top-down and bottom-up proteomics — Hung CW, Jung S, Grötzinger J, Gelhaus C, Leippe M, Tholey A (2014)
• Molecular characterization of two novel antibacterial peptides inducible upon bacterial challenge in an annelid, the leech Theromyzon tessulatum — Tasiemski A, Vandenbulcke F, Mitta G, Lemoine J, Lefebvre C, Sautière PE, Salzet M (2004)
• Macin family of antimicrobial proteins combines antimicrobial and nerve repair activities — Jung S, Sönnichsen FD, Hung CW et al. (2012)

Browse all ASH-analysed research →