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Compstatin inhibits complement and cellular activation in whole blood in two models of extracorporeal circulation
1Department of Clinical Immunology and Transfusion Medicine, University Hospital, Uppsala, Sweden.
Insights
Compstatin, a synthetic peptide, effectively inhibits complement activation and prevents immune cell adhesion in extracorporeal circulation. This peptide shows promise for preventing biomaterial incompatibility and developing new oral anticomplement therapies.
Area of Science:
- Biochemistry
- Immunology
- Biomaterials Science
Background:
- Complement activation on biomaterials triggers adverse cellular responses.
- Compstatin is a synthetic peptide inhibitor of complement component C3.
Purpose of the Study:
- To evaluate Compstatin's effect on complement activation in extracorporeal circulation models.
- To assess Compstatin's impact on cellular responses, particularly polymorphonuclear leukocytes (PMNs).
Main Methods:
- Testing Compstatin in whole blood within extracorporeal circulation models.
- Measuring complement activation products (C3a, sC5b-9) and cell surface marker expression (CD11b, CD16).
- Utilizing surface plasmon resonance to confirm Compstatin's binding to C3.
Main Results:
- Compstatin significantly inhibited C3a and sC5b-9 generation and C3 fragment binding to surfaces.
- Compstatin abolished PMN activation and binding to biomaterials.
- Blood cell counts remained unaffected by Compstatin treatment.
Conclusions:
- Compstatin effectively prevents complement-mediated biomaterial incompatibility in extracorporeal circuits.
- Compstatin is a potential therapeutic agent for preventing adverse reactions during procedures like cardiopulmonary bypass.
- Compstatin serves as a valuable precursor for developing oral anticomplement drugs.
Abstract:
Recently, a C3-binding cyclic synthetic peptide (Compstatin) has been identified that binds to complement component C3 and inhibits complement activation. Here we have examined the influence of Compstatin on complement activation and its indirect effects on cellular responses in whole blood in two models for extracorporeal circulation. Compstatin effectively inhibited the generation of C3a and sC5b-9 and the binding of C3/ C3 fragments to the polymer surface. As a result of the inhibition of complement activation, the activation of polymorphonuclear leukocytes (PMNs; as assessed by the expression of CD11b) and the binding of these cells (CD16(+)) to the polymer surface were almost completely lost. In contrast, blood cell counts were not affected. Using surface plasmon resonance technology, we have confirmed that Compstatin exerts its inhibitory effect on complement activation by binding to native C3. These data show that complement activation, leading to activation and binding of PMNs to the biomaterial surface, can be abolished by the addition of Compstatin. The properties of Compstatin make Compstatin a promising drug for use in extracorporeal circuits to avoid bioincompatibility reactions, eg, during cardiopulmonary bypass, but also a favorable precursor peptide for the development of an anticomplement drug for oral use.