Biomaterials Tutorial

The Complement System

Mª Cristina L. Martins
Instituto de Engenharia Biomédica (INEB), Porto, Portugal

Complement activation is part of the primary host mechanism for the immediate recognition and elimination of foreign particles [1-3].The complement system consists of 30 soluble proteins that circulate in plasma in their inactive form. Like other body systems, such as coagulation and fibrinolysis, complement proteins can be activated enzymatically through a complex series of reaction steps (Figure 1).

Complement can be activated in two ways, by the antigen-antibody complexes (classic pathway) or by the adsorption of the protein C3 on foreign surfaces (alternative pathway). Both pathways result in the formation of a membrane attack complex (MAC), which creates holes in the plasma membranes of foreign microorganisms, causing cell lysis or destruction. The release of three activated complement proteins, C4a, C3a, and C5a, which are part of the normal inflammatory process, mediates an increase in the invascular permeability and attracts leukocytes to the site of activation [1-3]. C3b also induces the adhesion of leukocytes when it is bound to foreign surfaces.

On biomaterials surfaces, complement activation generally occurs via the alternative pathway, by the adsorption of the protein C3 on the surface of the biomaterial. The classic pathway can also be induced by the biomaterial via the production of activated factor XII (XIIa) and factor XII fragments (XIIf) that are activators of the complement protein C1 [2].

Figure 1. Overview of the complement activation pathways. Adapted from Kubi [4].

References:

1. van Wynsberghe D, Noback CR, Carola R. Human anatomy and physiology. 3rd edition. WCB/McGraw-Hill; 1995.
2. Sapatnekar S,  Anderson JM. Hemocompatibility: Effects on humoral elements.  In von Recum AF, editor. Handbook of biomaterials evaluation: Scientific, Technical and Clinical Testing of Implant Materials, 2nd edition. Philadelphia, PA: Taylor & Francis; 1999. p. 353-365.
3. Dailey JF. Blood, 2nd edition. Ipswich, MA: Medical Consulting Group; 1998.
4. Kuby J. Immunology,  2nd edition W H Freeman and Company, 1994.