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Non-proteolytically activated C3 promotes binding of activated platelets and platelet-derived microparticles to leukocytes via CD11b/CD18
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. (Complement And Biomaterials)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
2012 (English)In: Immunobiology, ISSN 0171-2985, E-ISSN 1878-3279, Vol. 217, no 11, 1191-1191 p.Article in journal, Meeting abstract (Refereed) Published
Abstract [en]


We have previously demonstrated that complement component C3 binds to the surface of activated platelets, independent of proteolytic activation. The resulting form of C3, termed C3(H2O), was shown to be a ligand for recombinant CD35 (complement receptor 1, CR1). Previous studies by others have indicated that platelet-leukocyte complex (PLC) formation is dependent on the interaction between platelet exposed P-selectin (CD62P) and its ligand, PSGL-1, on leukocytes. In addition, CD11b/CD18 (Mac-1 or CR3) has been shown to participate in this reaction, but its ligand has not yet been identified.


To test the hypothesis that C3 bound to activated platelets and platelet-derived microparticles (PMPs) can act as a ligand for CD11b/CD18 (CR3) and contribute to PLC formation.

Methods and results:

Blood cells were depleted of plasma proteins. After extensive washing, C3 was added, and the leukocytes were activated with C5a and the platelets with thrombin receptor-activating peptide (TRAP). PLC formation was detected by flow cytometry (monocytes: CD14+/CD42a+, granulocytes: CD16+/CD42a+). For both granulocytes and monocytes, the addition of C3 significantly enhanced PLC formation. Formation of PLC was inhibited by both anti-P-selectin and anti-CD11b monoclonal antibodies. In addition, PMPs isolated from serum, were found to expose C3(H2O) and bind to leukocytes in a fashion similar to activated platelets.


We have identified proteolytically non-activated C3 as a ligand for CD11b in the formation of PLC and possibly the binding of PMPs to leukocytes. This observation most likely has pathophysiological implications for the recently reported links between thrombotic disease and the complement system.

Place, publisher, year, edition, pages
2012. Vol. 217, no 11, 1191-1191 p.
Keyword [en]
platelet activation, complement, platelet-leukocyte complexes, PMP, CD11b/CD18, complement component 3
National Category
Immunology in the medical area
Research subject
Clinical Immunology
URN: urn:nbn:se:uu:diva-123624DOI: 10.1016/j.imbio.2012.08.178ISI: 000311187800190OAI: oai:DiVA.org:uu-123624DiVA: diva2:315111
Aegean Conferences, XXIV International Complement Workshop, 10-15 October, 2012, Chania, Crete, GREECE
platelet mediated complement activation
Available from: 2010-04-28 Created: 2010-04-28 Last updated: 2013-11-14Bibliographically approved
In thesis
1. Crosstalk Between Activated Platelets and the Complement System
Open this publication in new window or tab >>Crosstalk Between Activated Platelets and the Complement System
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Several studies have shown that complement and thrombotic events co-exist. Platelets have been suspected to act as the bridge between the two cascade systems.

To study the platelet-induced complement activation we developed a system in which platelets were activated by thrombin receptor activating peptide (TRAP) in platelet rich plasma (PRP) or whole blood anti-coagulated using the specific thrombin inhibitor, lepirudin.

TRAP-activated platelets induced a fluid-phase complement activation measured as generation of C3a and sC5b-9, triggered by released chondroitin sulphate-A (CS-A) which interacted with C1q and activated the complement system through the classical pathway.

Complement components C1q, C3, C4 and C9 were also shown to bind to TRAP-activated platelets but this binding did not seem to be due to a complement activation since blocking of complement activation at the C1q or C3 levels did not affect the binding of the complement proteins. The C3 which bound to activated platelets consisted of C3(H2O), indicating that bound C3 was not proteolytically activated. Binding of C1q was partially dependent on CS-A exposure on activated platelets. The abolished complement activation on the surface of activated platelets was suggested to be dependent on the involvement of several complement inhibitors. We confirmed the binding of C1INH and factor H to activated platelets. To this list we have added another potent complement inhibitor, C4BP. The binding of factor H and C4BP was shown to be dependent on exposure of CS-A on activated platelets.

The physiological relevance of these reactions was reflected in an elevated expression of CD11b on leukocytes, and increased generation of platelet-leukocyte complexes. The platelets were involved in these events by at least two different mechanisms; generation of C5a which activated leukocytes and binding of C3(H2O)/iC3(H2O), a ligand to the intergrin CD11b/CD18 on their surface.

These mechanisms add further to the understanding of how platelets interact with the complement system and will help us to understand the role of the complement system in cardiovascular disease and thrombotic conditions.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 82 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 567
platelets, activated platelets, TRAP, chondroitin sulfate, C1q, factor H, C4BP, C3, Compstatin, complement, platelet-leukocyte complexes, platelet microparticles
National Category
Immunology in the medical area
Research subject
Clinical Immunology
urn:nbn:se:uu:diva-123681 (URN)978-91-554-7822-3 (ISBN)
Public defence
2010-06-01, Rudbecksalen, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, 09:15 (Swedish)
Platelet Mediated Complement Activation
Available from: 2010-05-11 Created: 2010-04-28 Last updated: 2010-05-24Bibliographically approved

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