The affinity of protein S to C4BP is several hundred-fold increased by calcium ions. C4BP is an acute-phase reactant, and its concentration in plasma may increase as much as four-fold. This does not result in free PS levels approaching 0 however, because C4BP exists in 2 forms: under normal circumstances, about 10 – 15% of the C4BP circulating in plasma lacks the b-chain and hence does not bind PS. During an acute phase reaction, the C4BP which lacks the b-chain is increased and therefore no significant decrease of free PS occurs.
C4BP is an octopus-like molecule which contains 7 identical a-chains and a smaller b-chain. There is one binding site for C4b in each of the a-chains, whereas protein S binds to the b-chain only.
The complement system is a complex system of serum proteins which interact in a cascade as part of the immune system. Complement helps antibodies kill invaders. Complement proteins mark any cells which do not have certain protective proteins on their outsides. The markers attract phagocytes (white blood cells that digest other cells) to destroy the invader, or can break the cell membrane of the invader. The classical pathway is activated by antibody-antigen complexes. C1-esterase is activated primarily by immune complexes containing IgM or IgG antibodies. The alternative pathway is initiated when a previously activated complement component (C3b) binds to the surface of a pathogen, where it is protected. Hence, the alternative pathway can be activated directly by foreign cell surfaces. Both pathways lead to the formation of a self-assembled membrane-attacking complex, which binds to foreign cell surfaces and induces lysis of these cells. C3 convertases are the key players in complement activation.