- It is estimated that one C3b deposited on an organ-
- ism can become four million in about 4 min.
- M. K. Liszewski and J. P. Atkinson14(p922)
The term complement refers to a group of serum proteins activated sequentially and rapidly in a cascade that produces molecules providing resistance to pathogens.14-16 The system was named in 1899 for its complementarity with antibodies in destroying microbes.15
Current nomenclature derives largely from the 1968 World Health Organization Bulletin “Nomenclature of Complement,”17 with subsequent modifications as mechanisms of action were further elucidated.
Three complement activation pathways are recognized: the classical pathway (activation by antibody), the alternative pathway (despite the name, the more phylogenetically ancient), and the lectin pathway. They culminate in a common terminal pathway. Components of the classical and terminal pathways are designated with a C and a number, reflective of the order of discovery of the component rather than the reaction sequence. (The prime, as in C′, has been discontinued.) Letters and abbreviations other than C typify the components of the other pathways. Complement component terms need not be expanded:
C1, C4, C2
factors D, B, P (P for properdin [“destruction-bringing”14])
Lectin or MBLectin
mannose-binding lectin (MBL), MBL-associated serine protease 1 (MASP-1), MASP-2, MASP-3
C5, C6, C7, C8, C9
C3 (common to all pathways)
Appended lowercase letters indicate complement fragments. Usually, a lowercase b indicates the larger, active (membrane-binding) fragment and a lowercase a, the smaller, release fragment (released on cleavage of the parent molecule). However, C2 is inconsistent: C2a is the larger active fragment and C2b the smaller release fragment. Other letters represent fragments of b fragments.
The subunits of C1 are as follows:
Various notations combining the C1 subunits convey the stoichiometry (relative quantities of subunits) of the complex; all such styles are acceptable:
Isotypes of C4 have capital letters appended:
Protein chains have Greek letters appended:
C3α is the α chain of C3.
Cleavage of C3α produces C3a and C3b.
iC3 or C3i
Complement components that form a complex are written in a series without spaces:
Sometimes a hyphen is used to indicate a series:
C5b67 or C5b-7
An asterisk shows nascent or metastable state:
Convertase complexes are linked complement fragments that activate other complement components. For example, the convertase that activates C3 is known as C3 convertase. As in the following examples, the convertases have different compositions, depending on which complement pathway generated them:
(Note: Occasionally, authors have changed the designation of the activated moiety of C2 from C2a to C2b, to be consistent with other complement components.18,19(p8) A tipoff to the change is the designation of classical pathway C3 convertase as C4b2b.)
A bar over the suffix was proposed in 1968 to designate activated complement, eg: but this convention has fallen from use.
Complement regulators include the following:
C1 inhibitor (C1-INH)
C1 esterase inhibitor, C1 esterase INH
C3 membrane proteinases
C4 binding protein (C4bp)
membrane inhibitor of reactive lysis (MIRL), membrane attack complex-inhibitory factor (MACIF), homologous restriction factor 20 (HRF20), P18, protectin
delay accelerating factor (DAF)
factor I [letter I, not roman numeral “one”]
factor H-like protein (FHL-1)
membrane cofactor protein (MCP)
(*Not the same as protein S; see 15.7.4, Hemostasis, Inhibition of Coagulation and Fibrinolysis.)
Complement receptors include the following:
complement receptor type 1 (CR1)
C3b receptor, CD35
C3d receptor, CD21, CD21S (short isoform), CD21L (long isoform)
collectin receptor; c prefix: collagen region of C1q
g prefix: globular head portion of C1q
factor H receptor (fH-R)