Description
General Description
Vitronectin (S Protein) binds to membrane attack complexes that fail to insert into membranes. The result is a soluble complex of S Protein and C5b-9 and this has been
named SC5b-9 (Dodds, A.W. and Sim, R.B. (1997)). Activation of complement in the absence of bilipid layer membranes results in most of the activated C5 forming SC5b-9
complexes. This can occur with activating particles such as immune complexes, yeast and bacterial cell walls. The SC5b-9 complexes can have more than one C9 (usually
three) and more than one S Protein (usually three) per complex. Thus, the typical molecular weight is ~1,030,000 Da. One C5b-7 complex can bind up to three molecules of S Protein.
If C8 or C8 and C9 have already bound to the C5b-7 complex three S Protein molecules will bind to these complexes as well. The C5b6 and C5b-7 complexes sometimes diffuse away from
the target cell and enter the membrane of a nearby cell. This is called bystander lysis or “reactive lysis” and can be a significant source of pathology. Binding of S Protein blocks
this non-specific lysis. Diffusion of these early complexes away from the activating surface may result in addition of C8 and C9 to the complex prior to S Protein binding.
Once S Protein binds to these complexes it prevents their membranolytic functions, thus creating soluble complexes that are subsequently cleared from circulation.
Physical Characteristics & Structure
The molecular weight of SC5b-9 Complex has a maximum approximate molecular weight of 1,030,000 Da and it is composed of ~13 polypeptide chains.
Variations in molecular weight may occur due to the fact that SC5b-9 complexes may have 1 to 3 C9 molecules and 1 to 3 S Protein molecules per complex.
Function
See General Description above.
Assays
SC5b-9 has no functional activity. Several commercial ELISA kits specific for SC5b-9 are available. These are sold by BD Biosciences, Techno clone Ltd, Quidel,
and HyCult Biotechnology. Most rely on capture of the SC5b-9 with antibodies specific for neo-antigens on the complex and secondary detection with antibodies to complement
proteins of the C5b-9 complex.
Applications
See General Description above.
In vivo
The normal serum concentration of SC5b-9 is low. Normal baseline levels for properly stored plasma range from less than 100 ng/mL to 600 ng/mL SC5b-9 or less
than 0.1% of maximal conversion. Elevated levels of circulating SC5b-9 complexes have been associated with bacterial infections and other diseases where complement
activation is known to occur.